“Epidemiology of pancreatic cancer: a global approach”

Wednesday 3 September 2014, 12.00 hours

“Clinical aspects of irritable bowel syndrome, with a special focus on visceral hypersensitivity and intestinal permeability”

“Formal and informal patient payments for public health care services in Bulgaria”

“Endoscopic treatment of obesity and metabolic disorder; Basic and Clinical studies on the effect of the Duodenal-Jejunal Bypass Liner”

The number of people who are overweight is increasing rapidly, as is the number of diseases associated with overweight such as diabetes and fatty liver disease. Weight loss surgery has been performed as a treatment for severely overweight individuals for many years. Recent research into less invasive techniques resulted in the Duodenal-Jejunal Bypass Liner (DJBL). This involves placing a flexible Teflon tube in the small intestine, just beyond the stomach, using laparoscopic surgery. This tube separates the flow of food from the digestive juices, thus delaying digestion. The DJBL is a highly promising technique: the study showed that patients treated with this technique lost weight and that their diabetes and fatty liver disease improved.

“Prevention of passive smoke exposure in children with a high risk of asthma”

“Protecting pre-license teens from road risk; Identifying Risk-contributing factors and quantifying effects of intervention Strategies”

Young people, and males in particular, die almost as often as a result of non-natural causes such as road traffic accidents as they do from diseases. This thesis shows that giving demonstrations or teaching basic rules of thumb as part of road safety education programmes does not prepare young adolescents (10–17 years of age) adequately for complex and dangerous road traffic situations. It is important for young people to practice in those situations in order to gain more experience, for example with a lorry’s blind spot. Moreover, it has been shown that short-term educational programmes, irrespective of whether they focus on promoting insight or fear, are less effective than originally thought.

Key words:

road safety, adolescents, education

“Hoe populaties personen worden”

“Modeling Non-Stationary and Stationary Mixed-Frequency Time Series”

The general public is continuously made aware of rising or falling future GDP growth rates, industrial production indices, unemployment rates, real wages and so on. The construction of these predictions, which are regularly done by central banks or research institutions, is usually based on the combination of various forecasts obtained using a large set of models. This dissertation fills two gaps in the mixed-frequency literature by introducing, applying and analyzing extensions of the Mixed Data Sampling (MIDAS) approach and mixed-frequency vector autoregressive models (VAR) to the non-stationary case on the one hand and by investigating causality testing within (large-dimensional) mixed-frequency VAR models on the other hand. The results of this thesis allow researchers to make more precise predictions of (non-stationary) time series such as GDP using predictors of potentially different frequencies.

Key words:

Econometrics, MIDAS, Mixed-Frequency, Time Series 

“Female Return Migration and Reintegration Strategies In Ethiopia”

“Macrophage polarization in atherosclerosis; from a black and white paradigm to a multicolored view”

Atherosclerosis, or hardening of the arteries, is a chronic inflammatory disease of the blood vessel wall and is the underlying cause of cardiovascular disorders such as myocardial infarction and stroke. It has been shown that macrophages (inflammatory cells) play an important role in the development and growth of plaques associated with the atherosclerotic process.
This doctoral research study examined the role of various subtypes of macrophages in atherosclerosis. There are two main subtypes: M1 macrophages encourage inflammation and are therefore assumed to worsen atherosclerosis, and M2 macrophages decrease inflammation and are therefore thought to slow down atherosclerosis.
We can thus conclude that macrophage polarisation plays an important role in the development of atherosclerotic plaque. It was shown that systemic M2 macrophage polarisation in mice treated with antigens from parasitic worms significantly reduces the growth of plaque in mice. These antigens could potentially be used in the future to slow down atherosclerosis.

Key words:

atherosclerosis, macrophages

“Information Disclosure: theory, policy and experiment”

“Instilling a thirst for learning; understanding the role of proactive feedback- and help seeking in stimulating workplace learning”

This thesis describes research on two important aspects of proactive learning behaviour: feedback-seeking behaviour and help-seeking behaviour. The results highlight the importance of promoting a psychologically safe working environment in which staff learning is stimulated and staff ask each other for feedback and help. Results show that supervisory staff play an important role, and that the quality of the feedback and help in particular is essential to performance. Moreover, the findings highlight the importance of investing in relationships and maintaining the accessibility of expertise. The challenge for organisations is to create a safe working environment that supports feedback-seeking and help-seeking behaviour. 

Key words:

learning, feedback, workplace, networking

“Health technology assessment of diagnostic strategies for Alzheimer’s disease”

People are trying to predict Alzheimer’s disease increasingly earlier. This thesis examines whether CSF diagnostics, applied in a decision algorithm, can improve the predictability of developing Alzheimer’s disease. This algorithm had no added value compared with established diagnostic practice.  It is possible that in the future, drugs may become available that slow down the progress of Alzheimer’s disease. Various scenarios were developed using a simulation model. This showed that a lumbar puncture can effectively help select patients that would benefit from this kind of hypothetical new drug.  The results of this study provide pointers to help better focus the diagnostics for Alzheimer’s disease.

Trefwoorden:

Alzheimer, dementie, cognitieve stoornis, diagnostiek, economische evaluatie, doelmatigheid, kosten-effectiviteit

“Cardiac Resynchornization therapy : maximizing benefits with minimal efforts"

“Clinical Optimization in Liver Surgery"

“Verwantschap weven : vertelpraktijken en culturele herinnering in transnationale adoptie”

“Vaccinating: self-evident or not ?; Development of a monitoring system to evaluate acceptance of the National Immunization Program”

This thesis describes the factors affecting parents’ decisions on immunising their children through the National Immunisation Programme in the Netherlands (RVP), and the experiences of child health care centre workers with the RVP. Attitude plays an important role in the parents’ decision regarding immunisation.  Most parents (81%) consider immunising their child within the RVP to be a matter of course. Child health care centre workers are satisfied with the way the RVP is currently organised. Some staff avoid any discussion with parents about the RVP, mainly due to a lack of time. Furthermore, we analysed messages placed on the Internet during the measles outbreak because this can serve as a consistent and quick source of information about people’s attitudes towards immunisation. All these various studies have resulted in a system being set up to monitor the acceptance of RVP among parents and child health care centre workers.

Key words:

National Immunisation Programme in the Netherlands, acceptance, parents

“Learning in Urology; designing simulator based skills; Training & Assessment”

Following the example set by the field of aviation, medicine is giving increasing attention to the use of simulation training, and also for surgical skills training. This thesis describes how simulators for learning surgical skills can be tested for reliability (validation) and how training using simulators can be structurally developed. In this project, and in collaboration with the urology department at Catharina Ziekenhuis Eindhoven and Radboud University Medical Centre, the ‘Program for Laparoscopic Urological Skils’ (PLUS) was developed and validated for the standardisation of basic laparoscopy skills for trainee urologists. On the basis of this study, the PLUS assessment has now been implemented as an obligatory examination for urology training in the Netherlands, and by the European Association of Urology as the Basic Laparoscopic Urological Skills exam. 

Key words:

simulation training, laparoscopy, urology

“Regulatory T cells in the pathogenesis of Multiple Sclerosis: potential targets for vitamin D therapy”

Multiple sclerosis (MS) is regarded as an immune disorder in which the immune system attacks the body’s own tissues and causes chronic inflammation of the brain. The exact cause of MS is unclear.  Both hereditary and environmental factors appear to play a role in developing one’s susceptibility to MS. In this study, we examined the population of T-cells, important immune cells, in the blood of MS patients and showed these to feature several defects.  We also showed that vitamin D, which is made in the skin under the influence of sunlight, has the ability to correct some of the defects in the T-cell population. Further research is required to determine whether vitamin D could be used in the treatment of MS.

Key words:

Multiple sclerosis (MS), treatment, T-cell population, vitamin D

“When is migration a security issue?”

“Light my Fire; leven buiten de comfort zone”

“Competentiegericht opleiden en toetsen”

“Cell-based therapy for hypoxic-ischemic injury in the 
preterm brain”

Brain damage due to oxygen deficiency is common in premature babies. Unfortunately, there is no therapy with which to treat this damage. In this thesis, a model that very accurately imitates brain development in premature babies shows that stem cell therapy is effective in reducing damage in the immature brain as a result of oxygen deficiency.  This innovative experimental study will form the basis for future clinical studies examining the suitability of stem cell therapy in the treatment of brain damage in premature babies. These studies may help us to improve the quality of life for many children born prematurely with brain damage.

Key words:

Brain damage in premature birth, stem cell therapy

“Towards consistency of EU external policies? A Case Study on the European Commission”

The European Union deploys a multifaceted external action through its trade policy, development cooperation and its foreign policy notably. The coordination of these different activities challenges the capacity of the EU and of individual institutions to deliver a consistent message. Examining the Treaty, legal and decision-making instruments to ensure consistency, this dissertation focused on the European Commission’s capacity to coordinate EU external policies. In a changing political, institutional and legal context, the Commission has coped with a renewed coordination challenge. Facing internal and external pressures, its decision-making has evolved to counter the risk of inconsistency of its policy output.

Key words:

EU, external policies

“Exposure to antenatal inflammation – mechanisms of fetal adaption”

"Nutrition Economics Disease related malnutrition & the economic healthcare value of medical nutrition"

Disease related malnutrition is still highly prevalent in the Western world, and that also applies for the Netherlands. However, this ‘silent killer’, as it were, is not as clearly recognisable as the other major diet-related health problem of overweight/obesity, with all its consequences, including high health care costs. 
This thesis shows that disease-related malnutrition in adults and the elderly is already costing the Dutch health care system 1.9 billion euros annually, and this does not include the costs for children. Health economics calculations have shown that millions of euros can be saved on health care by treating patients correctly. Optimum nutrition plays a crucial role in this respect.
Finally, ‘nutrition economics’ is described as a relevant new area within the long established field of Health Economics. The general discussion includes an overview of the methodological challenges and the subsequent recommendations for nutrition economics practice and future research.

Key words:

disease related malnutrition, costs, nutrition economics

“Opoe op bezoek”

“Prognosis of Chronic Clinical Pain Conditions: The Example of Complex Regional Pain Syndrome 1 and Low Back Pain”

This thesis contributes important new evidence to three main areas of patient-centered care for non-specific low back pain and CRPS 1.
First it is shown that fear is a potentially modifiable psychological factor that influences both the prognosis and treatment success in patients with persistent low back pain. Fear may lead to fear of activity and avoidance, which leads to disuse and distress and results in a deleterious cycle.  Second a first systematic analysis of prognostic factors in patients with CRPS 1 was done, but more research is needed to fully identify early indicators of the course of CRPS 1.
Third it is shown that in randomized controlled trials for low back pain on average, only 50% of the known prognostic factors were reported. Therefore, all stakeholders should support a collaborative effort to obtain a consensus on disease definitions and outcomes, in an effort to support the collection of high quality data for patients with chronic pain conditions.

Key words:

chronic pain, non-specifik low back pain, CRPS 1

“Eye on Innovation”

Friday 26 September 16.30 hours

“An experimental model of Huntington’s disease: Validation & Stimulation”

“Communication and Reasoning on Clinical Teaching Teams; The Genres that Shape Care and Education”

“Private-Sector standards as technical barriers in International trade in goods: in search of WTO disciplines.”

Private-sector standards, i.e. the standards developed, adopted and applied by private players such as supermarket chains, transnational corporations, and manufacturers of goods, are playing an increasingly important role in international trade. Because they are developed, adopted and applied by private entities, these standards are not legally mandatory. However, due to the immense purchasing power of big retail chains and multinational corporations which apply such standards, compliance with these standards may become mandatory for suppliers in order to gain real market access. This PhD dissertation explores the “world” of private-sector standards, as well as those WTO rules which may be relevant for the regulation of these standards and for addressing the challenges they pose. It thus contributes to the clarification and the better understanding of the rules applicable to private-sector standards under the WTO legal framework.

Key words:

private-sector standards; technical regulations; non-governmental acts; WTO law; barriers to trade

“Job Insecurity during Organizational Change: A dynamic perspective on the explanatory mechanisms of job insecurity”

Organisational change gives rise to job insecurity. This dissertation analyses the reasons why and the circumstances in which job insecurity has negative effects. A research model is presented showing two independent but coinciding explanations for negative effects of job insecurity: justice and exhaustion. Therefore, job insecurity does not only lead to exhaustion, but also evokes feelings of injustice, because the social relationship between employer and employee is unbalanced. The results show that these relationships are very complex. The relationship between job insecurity and justice is significant during the initial stages of organisational change in particular, whereas the relationship between job insecurity and exhaustion is most clear during the middle stages of organisational change. The results also indicate that employees who feel insecure about their jobs perform worse, if they think changes are communicated insufficiently. Proper management of organisational change is important and requires a tailor-made approach in particular.

Key words:

organisational change, job insecurity 

“Old and Out? Age, employability, and the role of learning”

Old and out? Not necessarily! The research in this thesis shows how employees stay employable as they age. In contrast to common workplace stereotypes, one's chronological age per se does not matter. Instead, being open to future career opportunities and engaging in learning activities are essential. Especially one's social network of colleagues at work is a powerful source for learning. This, in turn, helps to remain attractive in the labour market. The implications presented in this research project help managers, policy-makers, and older individuals to thrive in midst of the demographic shift.

Key words:

employability aging employee, learning abilities

“The Ins and OUTs of Disc biology”

Back pain is a common and long-term problem worldwide. In general, the only intervention available is pain control. Although it is not clear why people develop back pain, it is known that spinal cells play an important role in this. Van den Akker developed some unique new models allowing these cells to be examined in more detail. It was shown that the spine contains two different types of cells: a sort of stem cell playing a key role in tissue maintenance and a cell causing damage to spinal tissue in certain circumstances. In the future, these stem cells may be stimulated to repair the affected spinal tissue.

Key words:

back pain, spine, stem cells

“Questioning the rater idiosyncrasy explanation for error variance by searching for multiple signals within the noise”

Medical trainees are assessed performing clinical tasks but the examiners’ ratings can be highly variable. It is assumed that examiners assessing the same performance should form similar judgments and provide similar ratings. As such, the psychometric models currently used to analyze the ratings assume there is a single point of consensus. This research, however, found multiple clusters of consensus within the variable assessments provided by examiners for a single performance. This finding was consistent across two samples of participants and two different methodologies. Finding more than one point of consensus challenges the use of psychometric models to analyze examiners’ ratings.

Key words:

rater cognition, medical education, rater-based assessment

“Cardiac Dyssynchrony; structural, functional, transcriptional and pharmacological aspects”

One-quarter of patients with heart failure suffer from a conduction disorder resulting in an impaired cardiac contractility and function. Pacemakers improving their prognosis and reducing their symptoms (so-called cardiac resynchronisation therapy or CTR) are not effective in one-third of these patients. In an attempt to understand the underlying mechanism, Van Middendorp discovered a biomarker that might predict the effects of CRT and the treatment of dyssynchronous heart failure. He also showed that antiarrhythmic drugs should be used even more carefully in people with heart failure who also suffer from a conduction disorder. Furthermore, he showed that Vernakalant, a new antiarrhythmic drug that had initially received a positive evaluation, reduced the pumping ability of the heart to the same extent as the conventional antiarrhythmic drug Flecainide. This study was partially funded by the Dutch Heart Foundation.

Key words:

heart failure, conduction disorder, biomarkers

“Exploration of the sustainability of innovations in hospital care”

This dissertation examines the sustainability of healthcare innovations following their active implementation in a hospital setting. Among other things, it evaluates the extent to which two surgical healthcare programmes that were successfully implemented in different Dutch hospitals are still part of the standard healthcare process years after the quality improvement project. It also presents factors that may influence the success of implementing sustainability. The insights in this dissertation are important for future quality improvement projects and research projects. Two innovations – a short-stay programme for bowel surgery (ERAS) and a short-stay programme for breast cancer surgery (SSP) – were evaluated three to six years after their successful implementation. Both programmes appear to have been reasonably well maintained. The respondents deemed the following aspects of relevance to the sustainability of the ERAS and SSP programmes: trust and faith in the innovation, application of the innovation in different contexts, the possibility to adapting the innovation to suit local needs, the possibility to modify the innovation, the institutionalisation of the innovation, and the short lines of communication within the multidisciplinary team. Grant: ZonMw efficiency research

Key words:

quality improvements, efficiency, implementation, innovation, healthcare, old routines

“Dissecting boundaries”

“Why have so few countries industrialised?”

When countries develop, their economies become industrial, meaning that the goods and services that they produce are increasingly more diversified and complex. Despite progress, many countries in the world have not industrialised yet. This thesis shows that industrial and macroeconomic policies play a key role for industrialisation. A quantification of industrial policy instruments in East Asia and Latin America shows that larger public investments in East Asia spurred industrialisation. The type of government intervention also mattered: by designing an effective policy mix and by targeting strategic industries, East Asian states were more entrepreneurial than Latin American states. Second, firms’ investment behaviours follow business cycles’ fluctuations: by influencing these fluctuations, macroeconomic policies prove to be significant determinants of firms’ investments.

Key words:

industrialization, industrial policies, macroeconomic policies, East Asia, Latin America

“Determinants of Professional Commitment to Environmental Sustainability”

“Economic Evaluations in Healthcare: Methodological Considerations and Applications on Cost-Effectiveness of ACE Inhibitor Treatment for Renal Disease Prevention”

“Adequate antimicrobial treatment in elderly patients”

This dissertation examines the use of antibiotics in elderly patients. Elderly patients use far more antibiotics than younger patients. While the same standard dosages are prescribed for all adult patients, elderly patients tend to have a higher concentration of antibiotics in their blood than younger patients. This is caused by reduced creatinine clearance of the antibiotics as a result of renal impairment. Like children, older patients require a modified dose of antibiotics. Adjusting this dose in older patients can be difficult because it is hard to make an accurate assessment of renal function in these patients, and because of significant individual differences among these patients. This study provides a number of recommendations for adjusting the dose of various types of antibiotics.

Key words:

antibiotics, elderly patients, dose

“Economic preferences and attitudes; Origins, behavioral impact, stability and measurement”

Economic and social preferences such as e.g. risk preferences, trust or reciprocity are at the basis of human decision making. Advances in behavioral economics have documented the heterogeneity in those preferences among individuals and opened up a field of economics that is concerned with the drivers and channels of human motivation. This thesis discusses selected issues on the origin of preferences, their impact on (economic) outcomes, as well as methodological issues, such as the measurement of preferences and their stability over time. 

Key words:

economic behavior, decision making

“Strategy, Division, and Competition”

“The treatment of enterocutaneous fistulas and their metabolic sequelae”

Enterocutaneous fistulas are abnormal connections that develop between the intestinal tract and the skin and constitute a severe form of intestinal failure. They usually occur as a complication of abdominal surgery. In addition to being associated with several other complications, these fistulas have a mortality rate of 10% in specialised centres. This dissertation demonstrates the importance of a structured treatment guideline that is focused on sepsis treatment, optimising nutritional status, providing good wound and stoma care, and allowing enough time before proceeding with surgical options. We noted good quality of life in the long term and were the first to demonstrate how liver failure can occur as a complication of intestinal failure.

Key words:
enterocutaneous fistulas, intestinal failure, treatment

“Survival of the fittest plastics”

“Effects of botulinum toxin A injections and bimanual task-oriented therapy on hand functions and bimanual activities in unilateral Cerebral Palsy”

Children with unilaterally impaired hand function due to spasticity tend to use the affected hand less and less during their development. This phenomenon is called ‘developmental disuse’. This dissertation shows that task-specific bimanual therapy is the first choice of treatment for the prevention of developmental disuse and the improvement of bimanual skills. In this type of therapy, the affected hand is forced to be used in tasks which are meaningful to child and parents, resulting in repetitive hand use in daily life. Botulinum toxin injections are found to reduce strain and improve the quality of movement, which is measured by an instrument specifically designed for this purpose. However, they are shown to have a negative effect on strength and to have no added value to the use of the affected hand in daily life.This dissertation was financially supported by the Johanna Children’s Fund (JKF), Rotterdam Children’s Rehabilitation Fund Foundation/Adriaan Foundation (KFA), the Phelps Foundation for Spasticity, the Vooruit Foundation, the Elisabeth Strouven Foundation and the Kanunnik Salden-Nieuwenhof Foundation.

Keywords:

botulinum toxin (Botox), task-specific bimanual therapy, children with impaired hand function due to spasticity

“Get moving! Self-management support using mobile technology; A monitoring and feedback tool embedded in a counselling protocol to increase physical activity of patients with COPD or type 2 diabetes in primary care: the It’s LiFe! study”

In the dissertations written by Sanne van der Weegen and Renée Verwey a newly developed motion measurement system is being described used as part of the care people suffering from diabetes or COPD are provided with. An evaluative survey carried out among twenty-four GP practices showed that patients tend to exercise an extra eleven minutes daily on average. The motion measurement system connects wirelessly to a smartphone and online coaching system. An app shows the number of minutes a patient has exercised in relation to his or her personal goals. In the GP practice, the nurse practitioner is able to monitor the exercise results by means of a coaching system. The study carried out by van der Weegen focusses on the development and usability testing of the app and the validation of the motion measurement system. This study is co-funded by ZonMw.

Keywords:
motion measurement system, app, exercise programme, diabetes, COPD

“Get moving! Self-management support using mobile technology; A counselling protocol extended with a web-based coaching system to promote physical activity in patients with COPD or type 2 diabetes in primary care: the It’s LiFe! study”

In the dissertations written by Sanne van der Weegen and Renée Verwey a newly developed motion measurement system is being described used as part of the care people suffering from diabetes or COPD are provided with. An evaluative survey carried out among twenty-four GP practices showed that patients tend to exercise an extra eleven minutes daily on average. The motion measurement system connects wirelessly to a smartphone and online coaching system. An app shows the number of minutes a patient has exercised in relation to his or her personal goals. In the GP practice, the nurse practitioner is able to monitor the exercise results by means of a coaching system. The study carried out by Verwey mainly focuses on the development of a supervision protocol for nurse practitioners and the development and testing of the online coaching system. This study is co-funded by ZonMw.

Key words:
motion measurement system, app, exercise programme, diabetes, COPD

“The effect of Lutein on the inflammatory pathways in age-related macular degeneration (AMD)”

“A blind man’s bluff: Choice blindness in eyewitness testimony”

“The role of the different Kunitz domains of TFPI in the down-regulation of the extrinsic coagulation pathway”

Haemophilia is a blood clotting disorder that delays clot formation and can be fatal in patients undergoing operations, accidents or injuries. It is caused by low levels of coagulation protein. Present treatment for haemophilia is to reconstitute patients with missing protein but it is an expensive treatment with a risk of developing side effects. Alternative approach is to inhibit the anticoagulants, the regulatory proteins who inhibit coagulant proteins when they are produced in excess. This thesis focuses on how to inhibit TFPI, one of the most important anticoagulant proteins. The mechanism of inhibition of coagulation proteins was studied at domain (small part of protein) level. This study contributes to the biotech or pharma companies to develop inhibitors that can help haemophilic patients to live longer with cheap medication and no side effects.

Key words:
haemphilia, treatment, protein

“Psychotherapy for Depression Works! But How? Investigating the Effects and Mechanisms of Cognitive Therapy vs. Interpersonal Psychotherapy for Major Depressive Disorder”

Depression is a serious health problem that is paired with significant functional limitations and high social costs. Both cognitive therapy (CT) and interpersonal psychotherapy (IPT) have proven effective in reducing the symptoms associated with depression. Unfortunately, these treatments do not offer sufficient relief for all people with depression, and the risk of relapse is extremely high. Improving these forms of treatment is therefore essential. An important step involves gaining a better understanding of the effects and mechanisms of both treatment interventions. This was the topic of a major treatment study among 182 adults with depression. The research findings reveal that CT and IPT had similarly positive effects on reducing the symptoms of depression and that these effects were greater than those in a control group that placed participants on a waiting list. Unfortunately, the underlying mechanisms of these therapeutic effects remain unclear.

Keywords:
depression, psychotherapy, effectiveness, underlying mechanisms, treatment research

“De Ruimtetoerist – vragen over technologie en toekomst”

“Cognition and Type 2 diabetes; the interplay of risk factors”

Type 2 diabetes is a risk factor for dementia. Over a period of twelve years, a more rapid decline in cognitive function was found in people suffering from diabetes compared to people who did not suffer from this disease. It was shown, among other things, that cognitive impairment in people suffering from diabetes was associated with high blood pressure as well as low blood pressure. In elderly women, larger amounts of fat and muscle tissue were found to be associated with a lower risk of developing dementia. In men, only larger amounts of muscle tissue were found to be associated with a lower risk of developing dementia. These findings could lead to new ways to delay or prevent dementia. Furthermore, it was shown that an impaired understanding of words was associated with the presence of cardiovascular disease, neuralgia and lower levels of physical fitness. Therefore, doctors should be aware of the level of education reached by their diabetes patients.

Keywords:

diabetes, dementia, cognitive function

“The effect of D&O insurance on managerial risk taking”

Excessive risk taking of managers is associated with corporate failure. Researchers argue that insurance against personal liability of a manager (Directors and Officers liability insurance) would weaken his incentive to take care and partly causes excessive risk taking. Because only little is actually known about D&O insurance, this thesis analyses how D&O insurance should work ideally and how it currently works. 
This thesis observes that: (i) The value of investment decisions seems to rise with D&O coverage when competitive pressure is high enough; (ii) the insured manager benefits banks, provided that the corporation purchases an average insurance coverage; (iii) the D&O insurer settles disputes differently than courts, taking into account the degree of bad publicity in the media; and (iv) in times of financial instability, D&O insurance is the best analysed compensation measure in safeguarding firm performance. Hence, smaller corporations that do not carry D&O insurance yet would greatly benefit from it. 

Keywords:

D&O insurance, manager liability, risk taking, corporate liability, risk aversion

“The Application of the theory of efficient breach in contract Law; A Comparative Law and Economics Perspective”

This thesis analyzes the theory of efficient breach in three different legal systems, including English sales law, European Union contract law and Chinese contract law. The existing legal systems provide contract parties with more solutions, other than “efficient breach” to avoid inefficient performance. Generally, all the three systems allow parties to stipulate liquidated damages for breach of contract and expectation damages are chosen as the basic damages measures by English law and EU law. In this sense, paying monetary equivalence to performance is one option to contract promisors for avoiding inefficient contracts. Besides shaping contract parties’ incentives to perform or breach a contract via remedy rules, all the three legal systems have set out specific rules dealing with the circumstances where performance of a contract is inefficient. 

Key words:

legal systems, contract, breach

“Creating new perspectives on work-home interface; A cross-cultural comparison of Malta, Serbia and the Netherlands”

Cultural context plays an important role in the way employees combine work and home duties. Insights in the role of cultural context are highly relevant for setting up effective interventions and policies to reduce negative work home interface and improve health and well-being of individuals. Data for the studies in this thesis were collected in Malta, Serbia and The Netherlands. Besides work and home characteristics, such as work demands and family situation, cultural context plays an important role. The role of culture is impacting the negotiation of combining work and home demands, and this negotiation is intertwined with the cultural norms and expectations, gender and age. Different aspects appear to be relevant in different cultures. For example, colleague support is important in the Netherlands, and in other contexts it is not. Convergence of policies at EU level will not contribute to better work-home interface. A culturally sensitive approach in policies and interventions is called for.

Key words:

work home interface, cultural context, Malta, Serbia, The Netherlands

“How cardiac myofibers keep pace; Mathematical Modeling Of Adaptive Myofiber Reorientation and Electromechanics”

In order to improve the diagnosis and management of heart failure, Pluijmert developed a 3D computer model of the human right and left ventricles. Next, tests on the CRT pacemaker were carried out, deciding the best position for the left ventricular electrode in particular. A CRT pacemaker has little or no effect in one-third of the patients who are eligible for this method. It was shown that the ability to pump blood was increased most when activation of the entire left ventricle took place as quickly as possible. This result could be achieved by placing the electrode in the middle of the left ventricular free wall. This is a different position from the one included in the current European and American guidelines on CRT.

Key words:

CRT pacemaker, 3D computer model, heart failure

“Crescentic glomerulonephritis in ANCA associated vasculitis”

ANCA vasculitis is an example of an autoimmune disease that affects the smallest blood vessels in the body. It is a rare disease that can result in kidney failure. This dissertation is a compilation of studies on ANCA vasculitis. As the level of initial kidney damage predicts whether kidney failure is likely to develop, early detection of the disease is of paramount importance. A substance in the blood called CTGF is indicative of kidney scarring, which also contributes to the development of kidney failure. Patients are at increased risk of developing thrombosis during treatment. Unfortunately, the majority of patients suffering from ANCA vasculitis have a genetic profile that leads to a rapid recurrence of the disease after treatment has finished.

Keywords:

autoimmune diseases, ANCA vasculitis, kidney failure

“Autophagy in hypoxia and radioresistance: Regulation and Functional implications”

As a result of an abnormal architecture of blood vessels in a tumour, some tumour cells are insufficiently supplied with oxygen and are surrounded by a hostile tumour environment hindering the effectiveness of treatments. These cells depend on a process called autophagy, in which they break their own cell components into elements reusable for the production of energy, for instance. This doctoral study shows that the ULK1 protein plays an important role in the autophagy process and the survival of tumour cells in an oxygen-poor tumour environment. This insight into the role of ULK1 protein could lead to new therapeutic strategies to make these cells more sensitive to a lack of oxygen and to improve treatment results, if radiation therapy is part of the treatment given to the patient. Furthermore, it was shown that the recycling effect of autophagy in irradiated tumour cells did not influence the levels of resistance to radiation therapy. Funded by the Dutch Cancer Society (KWF Kankerbestrijding), STOPhersentumoren.nl, the Zeldzame Ziekten Fonds and the European Research Council (ERC).

Key words:

cancer, autophagy, radiation therapy

“The odd one out: exploring the nature of the association between minority status and psychosis”

Minorities have a substantially increased risk of developing schizophrenia, a psychiatric disorder that is characterised by a distorted perception of reality. This dissertation supports the hypothesis that social exclusion can literally make people sick. A population study revealed that discrimination can increase the risk of psychotic episodes in homosexuals. A potential biological mechanism was also discovered: higher levels of the messenger substance dopamine were detected in the brains of a socially isolated group, in this case young people with hearing difficulties. These young people were also more susceptible to experiencing social anxiety in their daily lives. Contrary to expectations, this susceptibility to stress was not found in men of Dutch-Moroccan descent, despite this minority group being at an increased risk of developing schizophrenia.

Key words:
social exclusion, minorities, schizophrenia, psychosis

“Structural and functional aspects of sensory-motor Interaction in the urinary bladder”

Urinary incontinence is a social problem for various patients, particularly those with Alzheimer's disease. This dissertation aims to examine the sensory information and motor output of the bladder on a functional and structural level. A study was conducted using several animal models, including a model for Alzheimer's disease. Various sensory nerves were discovered in the bladder wall. Using functional studies, we were able to detect bladder contractions that indicate a local sensory-motor system in the bladder. We also discovered an unusual anatomy of the bladder wall and unusual urinary patters in the model for Alzheimer's disease.

Keywords:

urinary incontinence, Alzheimer's disease, sensory information, motor output

“Opgelucht door de eerste lijn”

“Accurate Non-Iterative Modelling and Inference of Longitudinal Neuroimaging Data”

In recent years, increasing efforts have been made to collect longitudinal neuroimaging data in order to study how brains change over time. However, the popular methods used to analyse such kind of data may not always be appropriate (e.g., overly sensitive to model misspecifications, difficult to specify adequately or prohibitively slow to compute) and may sometimes lead to erroneous conclusions.  Motivated by these shortcomings, in this dissertation, we have proposed and studied the use of an alternative method, referred to as “the Sandwich Estimator method”, and have demonstrated that it is a fast, easy-to-specify and accurate option to analyse longitudinal or repeated-measures neuroimaging data. 

Key words:
Neuroimaging, longitudinal data analysis, Sandwich Estimator

“Improving dietary intake patterns among adults; the potential of targeting self-regulation and environmental-level factors in Web-based computer-tailored nutrition education interventions”

“Aandeelhoudersverantwoordelijkheid: De positieve rol van de aandeelhouder en aandeelhoudersvergadering”

Shareholders have specific rights, duties, and responsibilities relative to their shareholding company and other stakeholders. This study focuses on the responsibility of individual shareholders and the shareholders' meeting. The prevailing view is that shareholders inherently represent their own interests. But how and to what extent is this assumption limited? This dissertation identifies and describes the relevant circumstances, namely: the size of the share, the power of the shareholder, the background of the shareholder, the nature of the company, the company's current situation, the nature of the governing legislation, and the decision to be made. It also describes the possibility for others to 'correct' the shareholder's behaviour.

Key words:

shareholders' meeting, responsibilities, interests 

“Rectal cancer: Steps towards tailored treatment”

Treatment options for rectal cancer include surgery, radiation therapy and chemotherapy. In recent years, there has been an increased interest in organ-saving treatment of rectal cancer. This dissertation is aimed at tailoring the treatment of patients with rectal cancer. Three aspects were studied, namely the use of PET scans to make radiation therapy more accurate, the development of models to predict reactions to radiation therapy and the intensifying of radiation therapy to increase the chances of the tumour reacting to treatment. PET imaging proved to be useful in making radiation therapy more accurate. Furthermore, it was found that reactions to radiation therapy can be predicted by using PET scans and blood samples, among other things.

Key words:

rectal cancer, treatment, PET scan

“Living Apart Together Across Borders; How Ghanaian couples form, transform, or dissolve in the context of international migration”

The prevailing notion that all migrants in the Netherlands want to unite their families by bringing the rest of their relatives here demonstrates a lack of understanding for the familial context in which these migrants live. This study on Ghanaian couples and families shows that long-term family relationships can be maintained across borders, sometimes with respect to the prevailing sociocultural practices in the country of origin. A restrictive migration policy, however, can undermine the constitution and maintenance of long-term transnational family relationships. A strict policy can also hinder the mobility of migrants (e.g. the high cost of residence permits, hard-to-obtain tourist visas, etc.), which makes it difficult if not impossible for migrants to visit family members in Ghana or for other family members to visit the Netherlands.

Key words:

migration, Ghana, family relationships

“Modulation of protein – protein interactions in inflammatory diseases”

“(Epi)genetic profiling of cutaneous melanoma: Diagnostic, prognostic, and biological relevance”

Melanoma is the deadliest form of skin cancer. Due to the fast-growing number of patients suffering from this disease, melanoma is an ever-increasing health problem. Although current clinical evaluation of melanoma is mainly based on histopathology, there is still room for improvement in making the diagnosis and predicting the course of disease. This dissertation has assessed molecular changes in the DNA of melanoma, resulting in an improved understanding of melanoma biology. Furthermore, new biomarkers have been identified helping doctors make the correct diagnosis and predict the course of disease. These new markers can contribute to the determination of the optimal treatment of melanoma patients. 

Key words:

melanoma, diagnosis

“Causes and consequences of lipid overload in skeletal muscle, liver and heart”

With obesity, fat begins to accumulate in tissues other than adipose tissue (ectopic fat accumulation). This can have adverse health effects (lipotoxicity) and is believed to play an important role in the development of chronic diseases such as diabetes. This dissertation examined why fat accumulates in ectopic tissues such as muscles, the liver and the heart, and the role free fatty acids play in this process. It also examined the effect of fat accumulation on organ function. The study found that, while free fatty acids play a key role in the accumulation of fat, fat accumulation does not always lead to organ dysfunction. 

Key words:

obesity, ectopic fat accumulation, free fatty acids

“Evaluation of treatment for heavy menstrual bleeding”

Many women experience heavy menstrual bleeding. Two widely used treatments to drastically reduce blood loss are hormonal intrauterine devices and endometrial ablation to remove the endometrial lining of the uterus. This dissertation shows that women who underwent endometrial ablation were satisfied with the results five to ten years after treatment. However, it is unclear which of these treatment options is best. The research results will be available in a few years’ time. This dissertation found that different outcomes are being researched based on existing impact assessments, which makes it difficult to compare studies and inform patients properly. To do so first requires these outcomes to be determined and standardised in advance.

“Supply-demand balance in the atrium”

“The course of mild cognitive impairment and the role of comorbidity”

This dissertation studied the natural course of and the impact of comorbidities on cognitive decline in people suffering from mild cognitive impairment. The findings show an early decline in memory as well as a sharp or early decline in global cognition and executive control functions prior to the diagnosis of dementia being made. Furthermore, it was found that poor concentration/speed task results and a decline in the ability to perform such tasks are not indicative of the development of dementia. However, speed task results are linked to the severity of comorbidities. Comorbidities are likely to cause cognitive decline rather than result from an underlying neurodegenerative process. 

Key words:

dementia, cognitive impairment, course of disease, comorbidities

“Keeping warm in the cold; human brown adipose tissue upon cold acclimation”

This dissertation studied the effects of cold acclimation on slim and overweight/obese test subjects. Cold acclimation induced an increase in the production of brown adipose tissue. After stimulation, brown adipose tissue induced the conversion of glucose and fats into extra heat. Cold acclimation also increased energy expenditure without shivering. A significant relation was found between brown adipose tissue activity and energy expenditure without shivering. Furthermore, slim test subjects were found to grow accustomed to cold. Regular exposure to cold can, therefore, serve as a means of increasing energy expenditure, which may have favourable effects on weight maintenance. 

Key words:

overweight, brown adipose tissue, cold acclimation, energy expenditure

“Cardiovascular magnetic resonance; A key to imaging cardiac function”

“Investing in employability interventions ?’;Methodological challenges and economic evaluation results”

At some point, we will all experience work limitations due to health issues. In some cases, these limitations can lead to a reduction in work efficiency or absenteeism. In the Netherlands, the cost of absenteeism weighs most heavily on employers, who are expected to pay 70% of the absent employee’s salary for a maximum of two years. Various employability interventions have been developed to help minimise costs and facilitate reintegration. Interventions that focus on cooperation are the most cost-effective and therefore the most recommended. These include interventions that focus on the prevention and early detection of work-related health problems by encouraging an active role by company doctors and interventions that focus on employee-employer cooperation with the help of a mediator.

Key words:

employability, labour, healthcare, economic evaluation, cost-effectiveness

“A New Approach to Running Style Analysis using a Pressure-sensitive Insole Device: A small step towards injury prevention”

Running-related injuries affect about 50% of runners every year. Our running style could be a contributing factor to the occurrence of these overuse injuries. We used a pressure insole device to observe the effect of running speed on running style, to compare the running style of previously injured and uninjured recreational runners, and to observe the effect of minimalistic vs conventional running shoes. Continuous measurement allowed us to assess variability of running style from one stride to the other, which warrants further investigation in the area of running injury prevention. Prospective follow-up of runners also identified using multiple pairs of running shoes simultaneously and practicing other sports besides running as protective against sustaining an overuse injury.

Key words:

running-related injuries, insole device

“Asthma in Children: Towards Improved Monitoring Strategies”

“Improving conservative management of intermittent claudication”

Peripheral arterial vascular disease (PAVD) is a frequently occurring problem. In the Netherlands, 1 in 5 people aged 55 years and older suffer from this disorder. Charcot’s syndrome, commonly known as intermittent claudication (IC), is the first symptom of PAVD. Treatment of IC consists of supervised walking therapy (SWT), an invasive vascular intervention only being indicated if SWT does not have the desired results (from the patient’s perspective). However, not all patients are offered SWT in the Netherlands. Although there are many reasons for this, SWT not being covered by basic healthcare insurance is a key factor. Due to SWT not being fully covered, patients suffering from IC are exposed to an unnecessary risk of complications and death associated with much more expensive invasive treatment. Another important factor is a comparison between these treatments being difficult to be made due to a lack of good outcome measures. This thesis provides a first step towards a new outcome measure for the treatment of IC.

“The hypoxic tumor microenvironment: from imaging to targeting”

A lack of oxygen caused by poorly formed blood vessels is a common phenomenon in tumours. These oxygen-poor (hypoxic) areas are less sensitive to existing anti-cancer therapies such as radiation therapy and chemotherapy. This dissertation has shown hypoxic areas in tumours by using PET imaging technology. The characteristics of three clinical hypoxia PET tracers were compared with each other in a preclinical tumour model. Next, the combination of a new drug specifically aimed at these hypoxic areas and radiation therapy was tested in a preclinical setting. The results being promising, a phase I study will be set up shortly to test this combined treatment on patients.

“The nature of mutual recognition in European Law; Re-examining the notion from an individual rights perspective with a view to its further development in the criminal justice area”

This dissertation includes a comparative study of the nature of mutual recognition in European law within the framework of the European arrest warrant, among others. One of the conclusions is that mutual recognition does not mean a judge should blindly implement a ruling made by another Member State. After all, people have rights; especially when extradition is requested for minor offenses or in the event of poor prison conditions in the issuing Member State. If we hope to improve human and civil rights in Europe, judges should intervene when these rights are in danger of being violated.

“The thymus: when a rudimentary organ becomes active”

Maastricht University Medical Centre is a specialist centre for the surgical treatment of thymomas and the treatment of the muscular disorder myasthenia gravis (MG). Thymoma removal by means of robotic surgery proved to be a safe and reliable treatment option based on an analysis of all patients who underwent a robotic thymectomy between April 2004 and April 2012. The study also examined the role of robotic thymectomy in the treatment of MG among 125 patients. This form of treatment appeared to be safe, with a low morbidity rate and mortality rate of zero. After a median follow-up study 33 months later, 77% of MG patients had improved neurological function and nearly 33% of patients were in remission. This study also describes the discovery of the human polyomavirus in 39 thymomas.

“The Margins of Discretion in European Expulsion Decisions”

Foreigners who have been convicted of crimes and are subsequently issued with an expulsion decision have to leave a state which might have become their home and are often barred from returning to this state for a considerable period of time. An expulsion decision can constitute a severe interference with the private and family life of the individual and has the potential to destroy his or her personal, cultural, social and economic ties in that state. In light of these serious consequences, an expulsion decision should only be issued if it meets certain requirements. This research assesses whether the national (German and Dutch) law on expulsion complies with the standards set by European law. It identifies shortcomings in national statutory provisions on expulsion and provides recommendations for its reorganisation. 

“High-sensitivity cardiac troponins in heart and kidney diseases: from lab to clinic”

“The Evolution of beliefs and strategic behavior”

“Improvements Towards Safer Extraglottic Airway Devices”

Each year, approximately 250 million people undergo a surgical procedure under general anaesthesia. During anaesthesia, it is essential to secure an airway. In 60% of the cases this is done using a laryngeal mask. However, selecting the right laryngeal mask and securing it correctly is not always easy given the anatomical differences in patients. Furthermore, the wrong size and the incorrect placement of this mask can lead to aspiration problems and other complications. This dissertation compared 130 different laryngeal masks. It also studied various sizing methods and researched the potential correlation between anatomical parameters to find the best anatomical mask with the least complications. The dissertation also describes a new technique where specific laryngeal masks are used as a conduit for intubation.

Key words:

anaesthesia, laryngeal mask, safety

“Mechanism design for public goods, exclusive private goods and subcontracting”

Economic interactions such as selling an item for profit or scheduling the time of a subcontractor for cost savings can be formulated as a game. For such games this thesis studies and constructs mechanisms (set of rules) that coordinate the involved individuals to a good outcome despite the fact that they act in their own self-interest. These mechanisms are outputs of optimization models in which a good outcome can mean that the profit or the time saving is the highest possible. We consider also mechanisms that exhibit other useful properties such as simple and intuitive rules or easy implementation for a small sacrifice in profit.

Key words:

mechanism design, auctions, optimization

“Beliefs, Intentions, Power; essays on dynamic decision problems”

In this thesis individual and collective decision making is being researched. For individuals prone to procrastination or impulsivity, this work suggests that researchers and therapists should focus on the discrepancy between intentions and beliefs. For example, addicts could keep intention-belief diaries, where they specify how they want to behave, and how they think they will.Collective decision making is also intricate, as selfish free riders often take advantage of cooperative individuals’ efforts. This research shows that groups tend to select leaders who can force free riders to cooperate. Such self-organized hierarchies enable groups to achieve better outcomes.

Key words:

decision theory, game theory, optimality, dynamic inconsistency, public goods, cooperation, hierarchy

“Cell damage, inflammation and wound healing in major gastrointestinal surgery”

“De tijden veranderen – nu wij nog … ”

“Addressing the intentional destruction of the Environment during warfare under the Rome stature of the international criminal court”

Acts perpetrated during the course of warfare have, through the ages, led to significant environmental destruction. Until recently, such acts were generally regarded as an unfortunate but unavoidable element of armed conflict. The existing international rules have largely been ineffective and inappropriate. However, as the significance of the environment has come to be more widely understood and recognised, this is no longer acceptable, particularly given the ongoing development of weapons capable of widespread and significant damage. This dissertation therefore examines the current international legal regime relevant to the intentional destruction of the environment during warfare, and argues that such acts should, in appropriate circumstances, be recognised as an international crime and should be subject to more effective rules giving rise to international criminal responsibility. It also suggests a framework within the Rome Statute of the International Criminal Court as to how this might be achieved.

Key words:

warfare, international legal rules, crimes against the environment

“Intensive and Home Hemodialysis; acute effects and Long-term outcomes”

Most patients with terminal kidney failure undergo hemodialysis three times a week in a hospital. Hemodialysis can also be done at home, which allows for longer (night) and more frequent (intensive) dialysis. In addition to the known benefits of intensive home hemodialysis on life expectancy, quality of life, and cardiovascular functioning, this dissertation demonstrates additional advantages. These include increased stability of blood pressure and heart function, improved waste removal during dialysis, and protective effects in pregnant women and older dialysis patients. Finally, this dissertation also reveals that intensive home hemodialysis can reduce costs compared to traditional hemodialysis offered by hospitals.

Key words:

kidney failure, (home) hemodialysis

“Occupational asbestos exposure and cancer risk:A population-based approach using job-exposure matrices”

“Anterior Cutaneous Nerve Entrapment Syndrome Epidemiology and surgical management”

Chronic abdominal pain is sometimes caused by entrapment of a small cutaneous nerve at the ventral portion of the abdomen (anterior cutaneous nerve entrapment syndrome = ACNES). There is hardly any information available about this unknown syndrome. The incidence of ACNES and the effectiveness of treatment options have never been examined, for instance. This dissertation shows that 1 out of 50 patients presenting with acute abdominal pain to the emergency department suffers from ACNES. In the Netherlands, approximately 10,000 new cases of ACNES are diagnosed each year. Nine out of 10 patients experience considerable pain relief or become pain free following injections or minor surgery. Early diagnosis will lead to a massive reduction in health care costs.

Key words:

abdominal pain, abdominal wall pain, intercostal neuralgia

“Stigma by association; among family members of people with mental illness”

Stigmatisation essentially paints a group of people in a negative light and makes them more susceptible to social disapproval. This dissertation primarily focuses on the stigmatisation of family members of people suffering from a mental illness. They are often viewed as irresponsible, incompetent, strange or genetically contaminated. They are often blamed for causing the illness or for impeding the patient’s recovery. Stigmatisation can cause family members to become ostracised, ignored or treated poorly. This causes family members to feel lonely, isolated, abandoned or not taken seriously. Research has been conducted on how family members can reduce the negative consequences of stigmatisation. Recommendations were given in the field of information provision, education and support.

Key words:

stigmatisation, relatives of people with mental illnesses

“Using evidence of multiple study designs in systematic reviews”

“Innovative strategies for intermittent claudication – Towards a stepped care approach and new outcome measures”

“Market Access Issues in International Food Trade; Shrimp exports from Benin to the EU”

“L’Application des Textes de l’ohada aux entreprises Publiques: l ‘exemple de l’ausc et gie”

“Diet, postprandial metabolism and endothelial Function: effects of lutein-enriched eggs and trans-resveratrol”

“Nooit meer snijden!”

“Patient cost-sharing for health care in Europe”

“The economic and social effects of remittances and return migration in conflict-affected areas: the case of Burundi’”

This dissertation studies the effects of remittances and return migration on households and communities in Burundi and shows that in a conflict-affected country such as Burundi, which is one of the poorest countries the world, migration does not have the anticipated development-boosting effect that comes forward from the policy and academic literature on migration and development. The economic development impact of remittances, for example, was limited because remittances did not reach the citizens who needed it the most.  Similarly, return migration led to structural inequalities between return and non-return households in terms of land ownership and was found to negatively affect the living conditions of non-return households as well. The findings of this research highlight the necessity of a basic level of development before migration can positively affect development. 

Key words:

migration, development

“New Biomaterials Derived from poly (lactic acids); novel approaches to combine biodegradation, X-ray Contrast and Controlled Local Drug Release”

“Natural Hazards and Education; the impact of Floods on Primary School Education in Zambia”

The study has been designed to investigate how floods affect primary education in the flood plains in Zambia. Both qualitative phenomenological and quantitative comparative methods were used for the study. Two communities with primary school going children (those affected by floods and those not affected by floods within a 5 years period) were investigated and compared. It was found out that children in the flood plains compared to those in the upper land have low net school enrolment, the rate of repeating classes is high, dropout rate is high and performance in national examination is low. This will affect human capital and development in the flood plain environment in the long run.

Key words:

Floods, education, disasters, natural hazards, vulnerability, coping mechanisms

“Family-Member Migration and the Psychosocial Health Outcomes of Children in Moldova and Georgia”

This dissertation examined the relationship between family-member migration and the psychosocial health of children remaining in the origin country. Using survey data collected in Moldova and Georgia, analyses revealed that child-migrant separation does not correspond to universally negative child emotional health outcomes. In Georgia, no form of family-member migration corresponded to unfavourable psychosocial health outcomes; in Moldova, only the migration of a father corresponded to worse outcomes, and only among boys. These results suggest that the potential impacts of migration on child psychosocial health are heterogeneous and shaped by factors such as the gender of the migrant and child.

Key words:

family-member migration, impacts

“Teacher-based reactivity to provincial large-scale assessment in Canada”

Centralized testing is an integral part of public school education in many countries around the world. Policy-makers often have high expectations that accountability-based evaluation will inspire teachers and students to perform their best. Using the ten provinces of Canada as examples, this study examined if teachers do react to these large-scale tests, and in what ways. Results showed that teachers are quite reactive to assessment data across all the provinces, although the degree and types of instructional changes differed. More generally accepted instructional changes are correlated to positive attitudes about testing, the sharing of data, division-level supports, perceived pressure, and age. Teaching to the test, which denotes less generally accepted instructional practices, is more common and correlated with the return of more kinds of data, perceived pressure on teachers, and teaching at higher grade levels.

Key words:

school education, Canada, centralized testing, teacher’s attitude

“Parents’enabling the participation of their child with a physical disability: Actions, challenges and needs”

Of the 80,000 children in the Netherlands with a physical disability, many encounter daily problems with social participation. Parents appear to have a significant and positive influence on this participation. This dissertation found that we can learn a lot from these parents’ experiences. The actions, challenges and needs of parents primarily focus on the barriers to participation in the physical environment (e.g. limited access to schools, shops and playgrounds) and the social environment (e.g. negative attitude of others, lack of knowledge among teachers or sports instructors). This experiential knowledge is relevant for our modern participation society.

Key words:

children with physical disabilities, participation, parents

“the never-ending project; understanding E-government Project Escalation”

Public information technology (IT) projects are characterised by the numerous problems encountered during the realisation of the projects. This is demonstrated by major overspending resulting in the desired outcome not or only partially being achieved. This dissertation provides an insight into the escalation of commitment in public IT projects, a process in which a project is persisted in despite being shown not to achieve the desired outcome. Causes of this process as well as ways to prevent these are shown. Furthermore, it is examined how the escalation of commitment problem can be solved in a political environment.

Key words:

government, IT projects

“Tracking students in secondary education; Consequences for Student Performance and Inequality”

This dissertation examined whether the classification of secondary school pupils into different academic levels (e.g. VMBO (preparatory secondary vocational education), HAVO (senior general secondary education), VWO (pre-university education)) improves academic performance and whether it influences the academic opportunities. For instance, we found that pupils who are about to transition to HAVO or VWO perform better at VWO level and that pupils with highly educated parents receive better academic advice from their teacher in group 8 than their academic performance warrants. We also found that early learners are often categorised at a lower academic level than late learners, and even more so in countries with early selection criteria. This additional misallocation in countries with early selection has little impact on the long-term outcomes like final academic level or salary scale.

Key words:

academic level, academic performance, inequality

“Understanding the Clinical, Immunological and Genetic Molecular Mechanisms of Keratoconus”

“Philanthropie dynamique’; over de Sociologische betekenis van de herintrede van een sector’”

“Teamwork of clinical teachers in postgraduate medical training”

This dissertation examines the teamwork between medical specialists that train resident physicians. The way these specialists function as a team of academic trainers can be improved, certainly given the fact that they tend to be too task-oriented. The formal educator is too often seen as a super-teacher, who takes on the majority of the teaching load. There is little room for giving feedback, resolving conflicts, and working towards a collective ambition. An effective medical training group works towards structurally improving postgraduate medical education with a secondary aim of improving patient care. This dissertation recommends developing a validated digital evaluation tool that medical specialists can use to evaluate teamwork in training groups.

Key words:

postgraduate training for medical specialists, teamwork, feedback, leadership

“Cellular and molecular aspects of weight regulation: The adipose tissue”

This dissertation studied the effects of a low-calorie diet on fat molecules and the impact of genes on body weight regulation. We discovered two different genetic variations (the FTO gene in men and the MMP2 gene in women) that predict a weight gain of at least 8 kilos over the course of a decade. Furthermore, it was shown that fat cells increase their ability to include higher levels of glucose and fatty acids following weight loss achieved with a diet. After three weeks, fat cells were found to be craving fat, a mechanism provoking old eating habits (the so-called yo-yo effect). Certain target groups, including people having a genetic predisposition, should therefore receive improved weight-loss and/or weight-maintenance counselling.

Key words:

obesity, diet, yo-yo effect, fat molecules, genetic predisposition

“Cellular and molecular aspects of weight regulation: The adipose tissue”

This dissertation studied the effects of a low-calorie diet on fat molecules and the impact of genes on body weight regulation. We discovered two different genetic variations (the FTO gene in men and the MMP2 gene in women) that predict a weight gain of at least 8 kilos over the course of a decade. Furthermore, it was shown that fat cells increase their ability to include higher levels of glucose and fatty acids following weight loss achieved with a diet. After three weeks, fat cells were found to be craving fat, a mechanism provoking old eating habits (the so-called yo-yo effect). Certain target groups, including people having a genetic predisposition, should therefore receive improved weight-loss and/or weight-maintenance counselling.

Key words:

obesity, diet, yo-yo effect, fat molecules, genetic predisposition

“Complexiteit in beeld: samen naar de Moleculaire‘selfie’”

“Over de snotneus van de psychiatrie”

“Inside the psychopathic mind; social cognition, Emotional experience, and affect regulation in psychopathy”

Psychopathy is a serious mental disorder that is thought to stem from emotional disorders. This dissertation exposes the nature of these emotional deficits in more detail. The findings reveal, among other things, that psychopathy is associated with reduced sensitivity to physiological signals that play a role in how emotions are perceived by the body. Interestingly, people with psychopathy do not experience limited emotional capabilities, such as interpreting the thoughts and emotions of others on a rational level or the ability to communicate emotions through facial expressions. These findings provide further opportunities for treating this complex disorder.

Key words:

psychopathy, emotion

“Robust Asset Allocation in Incomplete Markets”

“A network approach to response inhibition and Aggression; combining functional imaging and Non-Invasive Brain Stimulation in the study of impulse control”

This research focuses on the identification of neural networks within the brain responsible for inhibition, i.e. the holding back of impulsive reactions. By means of functional brain imaging we identified networks within the brain which are involved in response inhibition and aggression. These networks have substantial overlap within certain regions in the prefrontal cortex and subcortical structures.  When inhibiting inferior regions within the prefrontal cortex by means of Transcranial Magnetic Brain Stimulation (TMS), different forms of response inhibition (i.e. response restraint and response cancellation) were compromised. Applying this further, proactive aggressive behavior in males – on the other hand – could be decreased, when enhancing areas within the right prefrontal cortex by means of Transcranial Direct Current Stimulation TDCS. This is a promising step towards a better understanding of the neural mechanisms underlying aggression and impulsivity and might result in the development of directly brain-based interventions for impulsivity related disorders in the future.

Key words:

impulse control, response inhibition, aggression, neural networks, non-invasive brain stimulation

“Remix, cover, Mash; remediating Phonographic-Oral Practice Online”

Tens and sometimes hundreds of musical variations on and covers of many of today’s top 40 hits on the pop chart appear on websites such as YouTube. Generally, these music productions are made by hobbyists or enthusiastic amateurs rather than famous, established artists. Although these enthusiastic amateurs’ practices are often regarded as simple forms of copycat behaviour or easy ways to capitalise on famous artists’ success, this dissertation shows that such activities can be regarded as important forms of learning and experimenting. This knowledge is particularly relevant with regard to bringing nuance into the current debates on copyright, musical skills and online participation.

Key words:

remix, music, skills, participation

“Pregnancy after caesarean; current care, clinical prediction and risk counselling”

In the Netherlands, more and more women are giving birth by caesarean. This study shows that the guidelines that determine when to perform a caesarean are not always followed. Interestingly, the guidelines governing the type of delivery after a prior caesarean are only followed 15% of the time. Moreover, major differences exist between hospitals, often independent of patient characteristics. It can therefore be concluded that local policies are largely determined based on the opinions of individual healthcare providers and hospital policies. A decision-making tool has been developed to improve the quality of care. Gynaecologists can use this tool in the examination room to make the best decision in consultation with the patient about the type of delivery: a natural birth or a caesarean.

Key words:

quality of care, caesarean, guidelines

“Blood, bones and brains; peripheral biological endophenotypes and their structural cerebral correlates in psychotic disorder”

“The relationship between youth crime and education”

“The Idle Mind Never Rests; functional brain connectivity across the psychosis continuum”

“Living up to Standards; interoperability Governance and Standards Adoption in Government Information Networks”

This dissertation investigates the organisational adoption of standards for data exchange within inter-organisational governance networks. First, it finds that the standards adoption process is a complex interplay of multiple actors at organisational and inter-organisational levels. Second, it identifies key factors that determine adoption: the decision-making structure governing the standards, the characteristics of a network and its external environment, the efforts required for standards adoption and the results from this, the capacity and needs of the adopting organisations, and the characteristics of the standards. Third, it finds that more complex networks require more centralised governance of standards than less complex networks.

Key words:

e-governance, interoperability, network governance

“Smoking Prevention among Primary School Children”

“Regional Policies: Convergence, Trade, and the allocation of Public Capital”

‘α7 nicotinic acetylcholine receptors and memory processes: mechanistic and behavioral studies’

This dissertation focusses on the functioning of our memory. Various memory processes and the ways to examine these are treated. Furthermore, the role α7 nicotinic acetylcholine receptors (α7 nAChRs) play in various memory processes is discussed in detail. Receptors are proteins which in this case are located on the surfaces of brain cells. Specific molecules (such as drugs) may attach to these receptors. Subsequently, the receptors may cause the brain cells to react. Focussing on α7 nAChRs is therefore relevant with regard to the development of new drugs aimed at treating memory problems in Alzheimer’s disease and/or schizophrenia, for instance.It was found that the blockade of α7 nAChRs with very low doses of so-called selective antagonists results in an improvement in memory performance and memory formation in rodents.

Key words:

α7 nicotinic acetylcholine receptors, acetylcholine, memory, learning, animal models

“A Breath of fear; a translational approach into the mechanisms of panic”

Panic disorder is characterised by unexpected panic attacks. In this study, this symptom was induced experimentally by the inhalation of 35% carbon dioxide. It was found that the diastolic blood pressure in particular reflects the dose-dependent emotional reaction and may therefore be a biomarker for carbon dioxide reactivity. It is common knowledge that carbon dioxide provokes a more intense fear reaction in patients with panic disorder. The results of this study show that this phenomenon may be caused by increased brainstem sensitivity. Furthermore, it is demonstrated that certain genetic variations in genes coding for pH-sensitive channels are associated with a different level of sensitivity to carbon dioxide. In conclusion, we designed an animal model of panic tailored to the human model of panic, therefore improving the translation of animal results to humans and offering advantages with regard to the development and testing of new treatment options.

Key words:

panic disorder, carbon dioxide inhalation

“It’s all about that post; opportunities and challenges of sharing information online”

Users spend a significant amount of time broadcasting their thoughts and experiences through social media. But we know little about how sharing information online affects the individuals who post information. In this dissertation, this research gap is confronted by studying positive and negative consequences of sharing information online. One of the findings is that the act of writing reviews may foster self-reflection and personal development, however in some circumstances it may also cause reviewers to behave impulsively. Sharing information may make users feel vulnerable particularly when this information is used by firms to provide personalized services without their consent.

Key words:

social media, users

“Exercise capacity, muscle strength and fatigue in sarcoidosis”

Sarcoidosis is a disorder of the immune system most commonly affecting young people. Various symptoms may occur dependent on the organs involved. This study shows that problematic symptoms in patients suffering from sarcoidosis include fatigue, a decreased exercise capacity and muscle weakness. It also shows that these symptoms are persistent and have a great impact on patients’ quality of life. Treatment and early detection of these health restrictions by using physical tests such as a six-minute walk test are of vital importance. A physical training programme contributes to a reduction in fatigue symptoms and an improvement in physical functions as well as quality of life.

Key words:

sarcoidosis, exercise capacity, muscle strength, fatigue, physical training

“Het einde van de periode”

“Searching for the Sources of Inequality”

“Novel Inflammatory Biomarkers for the Early Identification of Heart Failure’

“Renal Cell Cancer: A molecular-epidemiological approach to unravel new pathways underlying disease etiology and prognosis”

Kidney cancer is the seventh most common cancer, yet its cause remains unknown. This dissertation examines the risk factors and physiological mechanisms that could play a role in the development of kidney cancer within the framework of a Dutch cohort study (NLCS). High salt intake was identified as a new potential risk factor for kidney cancer, particularly among participants with low fluid intake. The link between salt intake and kidney cancer could not be explained by the participants’ high blood pressure, but could be partially explained by genetic variation in the renin-angiotensin-aldosterone system (RAAS), which regulates blood pressure, salt intake and fluid levels in the kidneys. By classifying kidney tumours according to tumour heterogeneity based on epidemiological changes, we demonstrated that potassium intake increased the risk of kidney cancer in one group of tumours and reduced the risk in others. Risk factors can therefore differ as a result of tumour heterogeneity, which should be taken into account in future research.

Key words:

kidney cancer, causes

“The role of tissue factor pathway inhibitor in arterial and venous thrombosis”

“From home towards the nursing home in dementia; informal caregivers’ perspectives on why admission happens and what they need”

This dissertation explored reasons for admitting people suffering from dementia to nursing homes from the perspective of caregivers. It also studied the needs perceived by caregivers during this process. Caregivers cite reasons for admission predominantly related to the person suffering from dementia including aggression, wandering, an increased need for help and a deterioration in cognitive function. Reasons related to caregivers themselves are cited as well, although to a far lesser extent. Based on the results, it is recommended that healthcare professionals offer caregivers the support they need during the transition process their relatives go through. This means that caregivers should be eligible for receiving care or support after the admission as well. In addition, it is argued that healthcare professionals should listen carefully to caregivers’ opinions rather than decide what they need without asking them first.

Key words:

dementia, volunteer aid, admission

“Elusive citizenship”

“Making sense of environmental responsibility; Investigating environmental stewardship among retail employees and consumers”

It is not easy to encourage environmentally-friendly behaviour. This is largely due to the personal disadvantages in the short term outweighing the collective advantages in the long term. Creating a strong sense of environmental responsibility can help to encourage environmentally-friendly behaviour, otherwise known as environmental stewardship. This dissertation found that branch managers play a key role in creating environmental stewardship among retailers and explains how this leads to environmentally-friendly sales. It is also possible to encourage environmental stewardship among consumers by stressing an affinity with future generations and by drawing attention to the individual influence they have on the environment.
 

Key words:

environmentally-friendly behaviour, environmental stewardship, responsibility, consumer behaviour, retail

“Risks and Benefits of Regional Anesthesia in the Perioperative Setting”

This dissertation studied various risks and benefits of regional anaesthesia in the perioperative setting. In the Netherlands, the number of operations has increased from 1.1 to 1.4 million a year over the last decade. Therefore, the evaluation of optimal perioperative care including anaesthesia is highly important. Although large studies are needed to show anaesthesia safety, recommendations for practice are often based on small studies. Comparing regional with general anaesthesia is a limited approach which underestimates the potential benefits of combined techniques in high-risk populations. Another aspect is the development of improved postoperative pain management programmes for specific operations. Catheter functioning, for instance, can be affected by material characteristics. Until recently, no systematic studies were needed to obtain a European hallmark (CE hallmark) but the results of this study show the need for these types of studies.

Key words:

anaesthesia, regional anaesthesia

“Credit in the economy: small business default correlation and firms co-movements”

Small businesses play a crucial part in every developed economy. They employ about 50% of the workforce and are the engine of innovation. For this reason policy makers and regulators support financing small businesses’ operations to allow them to grow and show its potential. Through a series of studies about small business credit risk, we show that small business credit risk is predominantly related to firm characteristics rather than to economy or industry wide conditions. We find evidence that distress in a customer industry is linked to higher credit risk among the small business suppliers and that trade credit is an important channel transmitting distress from one firm to another.

Key words:

small businesses, credit risk

“Microvascular dysfunction and diabetes: a vicious cycle?”

“Robotics-assisted treadmill exercise for cardiovascular rehabilitation early after stroke”

“Selective stimulation of the subthalamic nucleus in Parkinson’s disease; dream or near future”

Patients suffering from advanced Parkinson’s disease are treated with deep brain stimulation of the subthalamic nucleus. In addition to favourable effects on movement some patients experience behavioural side effects. The aim of this doctoral research was to attempt to stimulate only the part of the subthalamic nucleus responsible for motor functions. Although the study showed that the motor area could not be strictly divided from non-motor areas, rapid technological progress will allow deep brain stimulation to be further sophisticated, which will lead to a better treatment for patients.

Key words:

Parkinson’s disease, deep brain stimulation

“Preeclampsia is more than a vascular disease”

“Bundle Branch Block and Benefit from Cardiac Resynchronization Therapy”

Heart failure is a common chronic disease caused by reduced pump function. Treatment is expensive and the mortality rate is high, particularly in women. One cause is the nonsynchronous contraction of the heart muscle. This can be corrected with cardiac resynchronisation therapy (CRT) via a pacemaker. This study found that, compared to men, women had a lower threshold criterion for CRT; benefited more from CRT, including fewer symptoms and a lower mortality rate; were offered CRT less frequently than men; and were underrepresented in clinical trials with no mention of gender-specific outcomes.

Key words:

women, cardiology, heart failure, cardiac resynchronisation therapy, death

“Critically III Older Patients Treated in Intensive Care Units: Long-Term Consequences”

This thesis examined the long-term consequences of treatment in an Intensive Care Unit (ICU) on older patients’ quality of life, healthcare resource utilization, and presence of the distressing symptoms of pain, anxiety and agitation. Study findings reveal that up to one year after the ICU stay, older patients report a good quality of life and do not experience increased long-term pain, anxiety or agitation as compared to a sample of age-matched participants. The study concludes that with sufficient healthcare resources for support, such as frequent contact with their general practitioner, easily accessible rehabilitation programs and home healthcare services, older patients  can recover to a level where they can live relatively independently at home and do not require cost-intensive institutionalization. This information justifies treatment of older patients in ICUs, and to plan for the provision of sufficient resources to support older patients living at home.

Key words:

intensive care treatment, older patients, long-term consequences

“Vascular dysfunction: at the heart of cardiovascular disease, cognitive impairment and depressive symptoms”

This dissertation focussed on the damaging effects of deterioration of vascular function on the body. It is shown that deterioration of function of large blood vessels (due to vascular stiffening), small blood vessels (microvascular dysfunction) and the lining of blood vessels (endothelial dysfunction) not only plays an important role in the development of cardiovascular disease, but also in the development of dementia and depression. Vascular dysfunction is therefore an important new lead for preventing and treating cardiovascular disease, dementia and depression. Various studies were used, including the Maastricht Study, the Hoorn Study, the AGES-Reykjavik Study and the Rotterdam Study.

Key words:

blood vessels, vascular dysfunction, cardiovascular disease, dementia, depression

“Methylglyoxal, the glyoxalase pathway and advanced glycation endproducts in type 2 diabetes and cardiovasculair disease”

People suffering from type 2 diabetes are more likely to develop arteriosclerosis and are at sharply increased risk of developing cardiovascular disease. A possible explanation is that in people suffering from diabetes a higher number of sugared proteins (advanced glycation endproducts) accumulate in vascular calcifications, a process with damaging effects. This dissertation describes the relation between higher blood levels of sugared proteins and a higher risk of developing cardiovascular disease in people suffering from type 2 diabetes. Higher levels of sugared proteins in vascular calcifications are linked to a higher degree of inflammation and tissue necrosis from arteriosclerosis. Inhibiting the formation of sugared proteins may prevent cardiovascular disease and measurements of sugared proteins may improve predictions of cardiovascular disease in people suffering from type 2 diabetes.

Key words:

type 2 diabetes, arteriosclerosis, sugared proteins, cardiovascular disease

“Translabial 3D ultrasound for diagnosing levator ani defects in women with pelvic organ prolapse”

“Faculty development for medical professionalism in an Arabian Context”

“Multi-Agent Learning Dynamics”

Within the field of artificial intelligence, multi-agent systems are used to model and solve complex problems in today's society. The complexity of such systems requires that individual agents have the ability to learn to optimise their own behaviour. An important challenge is to gain qualitative and theoretical insight into the dynamics of these learning multi-agent systems, as their results are often hard to predict in advance. This dissertation describes how methods from the field of evolutionary game theory can be used for this. These methods are then applied to systems such as social networks and the stock market.
 

Key words:

artificial intelligence, multi-agent systems, game theory

“Modulation of vascular inflammation; cell type specific effects by ADAMs and HDL”

Atherosclerosis is the main cause of cardiovascular disease. This dissertation focuses on regulating inflammation, a key factor in atherosclerosis, by modulating high density lipoproteins (HDL, or ‘good cholesterol’) and modifying proteins via A Disintegrin And Metalloprotease (ADAM) enzymes. We demonstrated that the presence of ADAM10 in blood cells and endothelial cells has the opposite effect on atherosclerosis. We also found that HDL had cell-specific effects, namely, anti-inflammatory effects on smooth muscle cells and inflammatory effects on macrophages. These cell-specific effects are important for developing targeted and patient-specific therapies.
 

Key words:

atherosclerosis, inflammation, enzymes

“Oxidative stress responses in hepatocarcinogenesis; Unravelling the mechanisms using a toxicogenomics approach”

“Clinical evaluation of pulsed electromagnetic field treatment for acute scaphoid fractures”

Scaphoid fractures are relatively frequently occurring fractures among young, active people. Failing treatment or treatment initiated too late may lead to serious health related, economic or social problems. This dissertation describes the effect of pulsed electromagnetic field (PEMF) bone growth stimulation on healing of acute scaphoid fractures. The aim of our study was to determine whether treatment with PEMF bone growth stimulation was better than current plaster treatment.
In conclusion, the use of PEMF bone growth stimulation was found to have no significant benefit and is therefore not recommended as it is more expensive than standard conservative treatment. However, the observed positive effects of PEMF bone growth stimulation on healing time of a subgroup of stable, non-displaced scaphoid fractures show the need to further conduct goal-oriented research into the effect of PEMF bone growth stimulation on the healing process of acute fractures.

Key words:

scaphoid fractures, treatment, PEMF bone growth stimulation

“Health Technology Assessment in Epilepsy; economic evaluations and preference studies”

A proper comparative assessment of costs, clinical effects and quality of life is needed due to an increase in healthcare costs. This dissertation describes research carried out into quality of life of patients suffering from epilepsy, preferences as to epilepsy diagnostics, cost of side effects and cost-effectiveness of the ketogenic diet, a treatment method for children suffering from epilepsy in whom drugs are not sufficiently effective. In order to support parents and children in following the diet a special ‘recipe website’ (ketogeenmenu.nl) was developed. After four months, seizure frequency was reduced by more than 50% in half of the children following the diet. In the control group, this result was achieved in only 18.2% of the children. However, no conclusive evidence was found regarding the cost-effectiveness of the ketogenic diet.

Key words:

cost-effectiveness, epilepsy, ketogenic diet

“Alles draait om de chemie”

“Interictal epileptiform acivity as a marker for clinical outcome”

“Influencing panic; Experimental and clinical studies into determinants of panic severity”

“Proactive coping post stroke: The Restored4Stroke Self-Management study”

In the Netherlands, 40,000 people suffer a stroke each year. After a stroke, people often have problems dealing with the changes they face. The Restore4Stroke Self-Management study examined whether it is helpful to teach people who have suffered a stroke and their partners proactive coping, in other words to teach them to anticipate potential unpleasant consequences of stroke while planning a goal. Although proactive coping was found to be an important indicator of psychosocial functioning after stroke, teaching such strategies to groups of people who have suffered a stroke and their partners did not result in increased proactive coping or fewer participation restrictions. Our results may be explained by the intervention not being implemented optimally or the effects of contextual, personal and therapeutic factors on the outcome of our intervention. Therefore, more research is needed into these factors.

Key words:

stroke, treatment, self-management

“Mineral dust induced pneumoconiosis: a pivotal Role for the inflammasome”

Pneumoconiosis is the world’s most common disease caused by the inhalation of dust. Pneumoconiosis is usually caused by exposure to crystalline mineral fibres and particles. This dissertation explores which genes are activated or eliminated after lung cell exposure to asbestos or coal mine dust and which mechanisms play a role in the development of such diseases. The ‘inflammasome’ protein was found to play an important role in the inflammation underlying this disease. In addition, it was shown that activation of this protein in lung cells in turn triggers reactions associated with tissue stiffening, a feature of occupational asbestosis and silicosis. Furthermore, it was found that this protein can also play a role in the development of the disease in miners suffering from pneumoconiosis. This study may contribute to the development of new drugs.

Key words:

asbestosis, silicosis, pathogenic mechanisms

“Lifestyle and Diabetes Type 2- Closing the evidence gap between research and practice”

“Leer me dansen: de tango tussen bio en materialen”

“Out-of-pocket patient payments and vulnerable population groups in Serbia”

The dissertation describes the financial burden provoked by out of pocket patient payments in Serbia. Patients in Serbia pay informally by giving money or gifts to the health care providers. Sometimes they are also asked to bring goods such as food or medicines into the hospital. The results from this dissertation show that all those payments impose a high financial burden for patients, particularly on vulnerable groups such as chronically sick. About 2,3% of the population pays more than 40% of its income on health care. In maternity care, besides the financial burden, we also observe lack of compassion towards women giving birth.

Key words:

payments, health care, Serbia

“Health literacy in the Western Balkans: The example of Albania and Kosovo”

Health literacy (HL), an essential determinant of health, is totally irrelevant to current health policy in Albania and Kosovo, two transitional Albanian speaking countries in South East Europe. Through a series of surveys in both countries, we argue that health literacy could be linked to both health determinants and outcomes with education being the most important modifiable risk factor of limited HL. The observed associations additionally suggest to increase the efficiency of current respective education systems and form a solid basis for the inclusion of HL measurement in the health policy agenda of both countries for guiding interventions to improve the health status of citizens in these communities.

Key words:

Albania, Kosovo, health literacy, socio-demographic factors, socioeconomic

“Self-direction in return-to-work: bottlenecks, facilitators and an intervention”

The Dutch employers’ organisations MKB Nederland and VNO-NCW recently suggested a reduction of wage payments to absent employees from two years to one. It remains to be seen, though, whether this measure will result in an adequate resumption of work, if no investments are being made in improving the collaboration between absent employees and their employers. The results described in this dissertation indicate a strained relationship between absent employees and their employers as a result of divergent goals (employees: recuperation, employers: resumption of work) and mutual distrust. Furthermore, the results show that making investments in a better collaboration between absent employees and their employers is cost-effective.

Key words:

employees, employers, sickness absence, resumption of work

“Credit Ratings & the Auditor’s Going-Concern Opinion”

“Vergeet niet dat je arts bent’; Joodse artsen in Nederland 1940-1945”

‘Do not forget you are a doctor’, a father impressed on his son when they were forced to say goodbye to each other, persecuted by the Nazis. The father referred to the privileges as well as the duties of a doctor. Jewish doctors were indeed privileged considering their relatively high chance of survival. Furthermore, it is shown that they often tried to fulfil their professional duties. Being thrown upon their own resources, they had to solve numerous new ethical dilemmas. They often tried to help others by using medical methods, however unorthodox, and offer resistance.

Key words:

medical history, WWII, Jewish doctors

“De omwenteling die niet kwam; verkenning van het Bestuursbeleid bij het ministerie van Binnenlandse Zaken”

In this book, twenty-four projects carried out during forty years of administrative policy are passed in review. The author evaluates these projects from the perspective of public administration, which expects a change from a more traditional hierarchical administration (government) to a more network-oriented administration (governance). Despite challenges, it was concluded that the administrative theory held by the Ministry of Home Affairs has remained traditional. Furthermore, there was no systematically developed view of the relationship between government and society, necessary for a modern administrative policy, between 1969 and 2009. The researcher compared the Ministry of Home Affairs with parliament and a specialist department, where no breakthrough to another managerial view was achieved either. As a result, Schrijver assumes that chances of introducing more effective managerial processes at government level have been missed.

Key words:

administrative policy, Ministry of Home Affairs

“Is it remotely possible ?; remote supervision of general practice registrars”

GP registrars learning and work in practice is usually supervised by co-located, experienced general practitioners. An alternative is needed in outback Australia and northern Canada for registrars working in solo practice; clinical supervisors use information and communication technology to supervise registrars remotely.  This research demonstrated this approach led to comparable outcomes in national examinations, and considered why it could work and for whom. To our surprise some registrars’ learning accelerated because of their clinical responsibilities, their freedom to choose the timing and resources for learning, and seeing the impact of their work through continuity of care with patients and communities. Continuity of remote supervisor meant their learning efficiently built on prior experience and considered the personal challenges and characteristics at the heart of providing effective health care.  Responsibility, continuity of care and continuity of supervisor, are key factors in effective and efficient postgraduate learning.

Key words:

medical education, General Practice, clinical supervision, rural and remote underserved communities, distance education

“Exercise training and physical activity in patients with mild to moderate COPD in primary care”

“Financial decision making in incomplete markets”

“Parenting across borders; Effects of transnational parenting on the lives of Angolan and Nigerian migrant parents in The Netherlands”

This study is about Angolan and Nigerian parents who live in the Netherlands, but whose children reside in the country of origin. It examines whether this separation effects the wellbeing of the migrant parent. The study reveals that transnational separation can indeed have a negative impact on the wellbeing of the parents. However, this separation does not have to be problematic if good family arrangements are made, such as maintaining regular contact with the child. Furthermore, the context of migration and integration proves a crucial factor. Undocumented migrants and migrants with a low socioeconomic status are particularly prone to reduced wellbeing, partly due to limitations in migration policy that can hinder physical contact with the child..

Key words:

migrant parents, transnational separation

“Technology-based measurement of arm-hand skill performance in daily life conditions”

Stroke patients and children with cerebral palsy tend to experience severe arm-hand problems in their daily lives. This dissertation aims to develop a tool to measure arm-hand performance in the home. The tool must be able to measure a) the activities to be performed, b) how often the arms and hands are used, and c) the quality of these movements. This measurement tool is important for evaluating patient progress, detecting arm-hand problems, adapting treatment to the patient’s needs, and assessing the effectiveness of new treatments.

Key words:

rehabilitation, measurement tool, arm-hand problems

“Abdominal Wall Hernia Repair; intraperitoneal Mesh and Adhesions”

One in five patients develops an incisional hernia after having undergone abdominal surgery. Such hernias are abdominal muscle defects allowing intestines to protrude. Hernia repair is performed by placing synthetic woven meshes. Adhesions are being formed between intestine and mesh in reaction to the placement of intraperitoneal meshes. These adhesions can lead to serious problems which are underestimated by surgeons. Experiments showed that mesh coatings can largely prevent this problem. Furthermore, three pills taken prior to surgery could halve the number of adhesions formed between intestine and mesh. Finally, a patient model was developed to further confirm our results.

Key words:

incisional hernias, postoperative adhesions

“Protective and adaptive responses by antioxidant flavonoids”

Radicals are harmful due to their potentially damaging effect on DNA and proteins, which causes ageing and cardiovascular disease. Antioxidants protect against radicals. A surplus of radicals results in adaptation, which means the body will produce more antioxidants. Flavonoids, antioxidants obtained from the diet or dietary supplements, can neutralise radicals. Flavonoids could increase the damaging effects of radicals as this neutralisation process could reduce the adaptation made by the body. This study shows that a product of the flavonoid formed during the neutralisation process also induces adaptation. Therefore, flavonoids protect against the damaging effects of radicals and cause adaptation to be maintained.

Key words:

radicals, antioxidants, flavonoids

“Prevention of obesity in childhood”

This dissertation examines whether the current rise in childhood obesity starts in the prenatal period and whether a secular trend in height can help explain why children have become heavier over the past eighty years. No prenatal secular trend was identified in this dissertation. A postnatal secular trend, however, was evident in terms of weight, height, and BMI. Small for gestational age (SGA) infants are more likely to develop obesity than normal birth weight infants. Furthermore, data on height and weight in a healthy Dutch population were used to develop a prediction model to determine the risk of developing childhood obesity in infants born at a healthy weight. This prediction model is an important tool that can be used in child healthcare to prevent obesity later in life.

Key words:

obesity, children, height, weight, prevention

“How humans economize; energy restriction and end energy expenditure”

“Essays on Working Hours”

“Tissue Distribution and Function of Arginase I: an experimental study”

“Failure to adapt”

The current dynamic social and economic context places additional demands on both the employee and employer. Workplaces require continuous adaptation. 6,6 % of employees are in job lock. 61,4 % of those employees stay in a long term job lock. Job lockers experience more physical and mental health problems compared to those employees who successfully adapt. For the companies job lock leads to increased costs due to withdrawal behaviours and decreased productivity and job attachment. The results from the dissertation are useful to HRMs and reintegration companies for detecting employees at risk to become job locked and building preventive and curative programs.

Key words:

adaptation, job lock, reintegration

“Cardiac Adaptation during and after hypertensive gestation”

“Small fibers, big troubles; diagnosis and implications of small fiber neuropathy”

“The Role of Incentives, Preferences and Personality in Decision Making”

“Tussen wiskunde en werkelijkheid”

“Mesenchymal stromal cells to induce tolerance to solid organ transplantation”

“Psychological adjustment to stress and trauma; Hippocampal configuration learning, cognitive emotion Regulation, and frontal brain asymmetry, as predictors of Resilience”

“Market Reactions to management earnings forecasts”

“Macrophages in Colorectal Cancer: proof of principle for diagnostic application”

“Orthopaedic Infections: pre-clinical models, diagnostic tools and novel coatings”

“Extra articular manifestations and comorbidities in spondyloarthritis: epidemiological and clinical aspects”

“Lokale overheid en populatiegericht gezondheidsbeleid”

“Zooming into the micro-level of experience: An approach for understanding and treating psychopathology”

“Poor Lending”

Why is it hard for the rich to lend to the poor? Mainly because it is costly and risky. This thesis addresses, in the context of microfinance, the challenges faced by financial intermediaries that lend to low income clients. Microfinance institutions can improve their efficiency by concentrating their efforts on their core mission, and find investors that share the same preferences with respect to social and financial objectives. Regulation aimed at facilitating the sharing of information between lenders can significantly reduce the risk of over-borrowing and thus reduce the risk of both lenders and borrowers.

Key words:

microfinance, risk, efficiency

“Compare care in oncolytic medication surveillance:pharmacovigilance, acceptability, risks and events”

“Hallux Valgus; preoperative criteria and surgical outcome”

Hallux valgus betreft een scheefstand van de grote teen, die uiteindelijk ook de rest van de voet kan beschadigen. Het dragen van schoenen met hoge hakken en smalle neuzen heeft aangetoonde invloed op ontwikkeling ervan. Het lijkt een klein probleem, maar  bij ouderen verhoogt het het risico op vallen. Chirurgische correctie van de teen biedt betere resultaten dan niet chirurgische behandelingen. Toch is er behoefte aan verbetering van de operatieresultaten.
Een belangrijke uitkomst van het promotieonderzoek is dat uit vele criteria er één gevonden is die een voorspellende waarde heeft voor het operatieresultaat, namelijk de grootte van de hallux valgus hoek op een röntgenfoto. Verder blijkt dat van de twee meest gebruikte operatietechnieken voor hallux valgus, de meest eenvoudige met de minste risico’s hetzelfde resultaat biedt dan de meer ingewikkelde. Deze verdient dan ook de voorkeur. 

Trefwoorden:

hallux valgus, behandeling

“Na het hartinfarct, wat dan?”

“The Computational Architecture of the Human Auditory Cortex”

“Hearing loss in young children; challenges in assessment and intervention”

Slechthorendheid bij kinderen is nadelig voor de spraak-, taal-, emotionele en sociale ontwikkeling. Meten van de juiste hoordrempel en tijdige gehoorrevalidatie is noodzakelijk bij, door hoorscreening aangetoond, gehoorverlies. Kinderen met ernstige binnenoorslechthorendheid zijn te helpen met een cochleair implantaat. Tegenwoordig worden ze steeds jonger geïmplanteerd. Te vroeg geboren kinderen kunnen slechthorend zijn door onvoldoende rijping van het gehoor. Voorzichtigheid is geboden bij te vroege implantatie. De hoorscreening gebruikt Otoakoestische emissies (OAEs): spontane geluiden uit een ‘functioneel’ slakkenhuis. Een meetinstrument is ontwikkeld om middenoordrukproblemen te optimaliseren zodat OAE’s beter te meten zijn. Dit meetinstrument leidt tot reductie van vals negatieve testuitslagen.

Trefwoorden:

slechthorendheid, diagnose, behandeling

“Aspects of the preoperative assessment in patients undergoing liver surgery”

Voor patiënten met levertumoren is een leveroperatie vaak de enige kans op een genezing. Sommige patiënten ontwikkelen postoperatief leverfalen. Door preoperatief het toekomstige levervolume en de restleverfunctie te voorspellen, kunnen patiënten met een verhoogd risico op leverfalen worden geselecteerd. In dit proefschrift werd aangetoond dat de computerprogramma’s ImageJ en Osirix®(gratis) geschikt zijn om het levervolume te voorspellen. Een goede restleverfunctietest bestaat nog niet. Ophthalmaat is een nieuwe potentiële biomarker voor leverfunctie. De waarde van ophthalmaat werd voor het eerst getest in een model tijdens een leveroperatie. Dit model is als zodanig nog niet geschikt als functionele levertest maar de resultaten zijn veelbelovend.

Trefwoorden:

levertumor, diagnose, behandeling

“Puzzling with the pathways of life”

“Intestinal Parasitosis and Under-nutrition in Ethiopia: Prevalence, Risk factors, and Prevention”

“Structural transformation and economic development: Can development traps be avoided?”

Dit proefschrift gaat over een klassiek onderwerp in de economie: waarom blijven sommige landen arm terwijl andere de levenstandaard van geavanceerde economieën bereiken en daarbij de achterstand op het gebied van technologie, inkomen en sociaal welzijn inlopen. Dit proefschrift stelt dat succes (of mislukking) van economische ontwikkeling nauw verbonden is met de mate waarin ontwikkelingslanden hun economische structuur kunnen transformeren en verschuiven richting de productie van goederen met eem hoger technologische niveau en een grotere vraag op de wereldmarkt. Een empirische analyse van de afgelopen 60 jaar uit een steekproef van 100 landen toont dat de succesvolste economieën (zoals China, Korea, Taiwan en Thailand) landen waren die de twee transformaties tegelijk konden realiseren. De minder succesvolle landen konden deze transformaties daarentegen niet realiseren en eindigden in de lagere inkomens of middeninkomens (zoals Brazilië, Malawi, Zuid-Afrika en Zambia), waar slechts een fractie van de maatschappij de vruchten kan plukken van de internationale stromen van technologische kennis.

Trefwoorden:

Economische ontwikkeling, technologische inhaalslag, structurele verandering

“The Politics of good food. Why food engineers and citizen-consumers are talking at cross-purposes”

Het maatschappelijke vertrouwen in technologisch bewerkt voedsel staat onder druk en is niet vanzelfsprekend. Een zinvolle publieke dialoog over de maatschappelijke impact van voedseltechnologie is een belangrijk ingrediënt voor het herstellen van dit vertrouwen. In dit proefschrift wordt het Nederlandse publieke debat over voedseltechnologie geanalyseerd (in het bijzonder over E-nummers) en verklaard waarom technologen en consumenten vaak langs elkaar heen praten. Wantrouwen ten aanzien van E-nummers gaat niet altijd over gezondheidsrisico’s alleen, maar ook over een omgang met voedsel die bijdraagt aan een onverschillige, gemakzuchtige en vlakke eetcultuur. In het proefschrift worden verschillende aanbevelingen gedaan voor verbetering van deze dialoog.

Trefwoorden:

voedsel, technologie, E-nummers

“Mechanisms of endogenous brain protection; Clues from the transcriptome”

“Integrating workplace learning, assessment and supervision in health care education”

Empirisch onderzoek bij studenten verloskunde en hun begeleiders leidt tot een nieuw onderwijskundig model dat omschreven wordt als een levenslange competentiereis. Dit nieuwe model benadrukt het bevorderen van een continue competentiegroei op de werkplek. De resultaten tonen aan dat reflectie een belangrijk onderdeel is van het professioneel handelen. Deze reflectie moet gekoppeld worden aan feedback maar het blijkt dat professionele begeleiders moeite hebben om kwaliteitsvolle feedback te geven. Tevens zorgt de hoge werkdruk in ziekenhuizen ervoor dat er naast de patiëntenzorg weinig tijd overblijft voor het bespreken van de door de student verzamelde informatie en hoe deze in de praktijk te gebruiken. Verder is het belangrijk dat de beoordeling gebeurt door een jury van experts die rekening houdt met de continue groei van de student. Uiteindelijk beslist deze jury of een beginnende professional veilige zorg kan verlenen aan de patiënt. Vanaf dat ogenblik is het aan de gezondheidsorganisaties om de levenslange leerlijn verder te faciliteren.

Trefwoorden:

gezondheidszorg, onderwijs, competenties

“Peripheral Neuropathy outcome measures; Standardisation (PeriNomS) study part 2: Getting consensus”

De Perifere Neuropathie uitkomstmaten Standaardisatie (PeriNomS) studie is een onderzoek naar uitkomstmaten voor aandoeningen van de zenuwen (polyneuropathie). Objectieve resultaten vergen een objectieve meetlat (uitkomstmaat). Hiermee kan namelijk worden bepaald hoe het met een patiënt gaat, en wat het effect is van een bepaalde behandeling. Helaas zijn er voor de meeste chronische aandoeningen geen objectieve maten beschikbaar. Het huidige onderzoek heeft geleid tot de ontwikkeling van zo’n meetlat, die internationaal ook is erkend als de beste manier om het effect van een behandeling te bepalen. Daarmee zijn toekomstige studies ook beter met elkaar te vergelijken. Deze methodiek is bovendien ook bruikbaar voor andere aandoeningen.

Trefwoorden:

perifere neuropathie, uitkomstmaten

“Health Benefits and social determinants of the mediterranean diet at a time of economic crisis: results from the moli-sani study”

De Perifere Neuropathie uitkomstmaten Standaardisatie (PeriNomS) studie is een onderzoek naar uitkomstmaten voor aandoeningen van de zenuwen (polyneuropathie). Objectieve resultaten vergen een objectieve meetlat (uitkomstmaat). Hiermee kan namelijk worden bepaald hoe het met een patiënt gaat, en wat het effect is van een bepaalde behandeling. Helaas zijn er voor de meeste chronische aandoeningen geen objectieve maten beschikbaar. Het huidige onderzoek heeft geleid tot de ontwikkeling van zo’n meetlat, die internationaal ook is erkend als de beste manier om het effect van een behandeling te bepalen. Daarmee zijn toekomstige studies ook beter met elkaar te vergelijken. Deze methodiek is bovendien ook bruikbaar voor andere aandoeningen.

Trefwoorden:

Mediterraan dieet, gezondheidsvoordelen, economische crisis

“Health Benefits and social determinants of the mediterranean diet at a time of economic crisis: results from the moli-sani study”

In dit proefschrift wordt het typisch mediterrane dieet geassocieerd met een vermindering van ontstekingen en het algemene sterfterisico voor diabetici. Italianen volgen dit gezonde dieet echter steeds minder. Naast sociale veranderingen leiden de hogere kosten van veel essentiële voedingsmiddelen uit het mediterrane dieet, zoals vis, fruit en verse groenten, ertoe dat mensen dit eetpatroon inruilen voor minder dure producten waarmee geld wordt bespaard maar die over het algemeen minder voedingswaarde hebben. De huidige economische crisis zal waarschijnlijk de socio-economische ongelijkheid vergroten en ongunstige gezondheidsresultaten veroorzaken, met name onder de minder rijke groepen.

Trefwoorden:

Mediterraan dieet, gezondheidsvoordelen, economische crisis

“The Killing of Death; Denying the genocide against Tusi”

“Molecular detection to improve surveillance of multi-resistant bacteria”

Dit proefschrift beschrijft het gebruik van verschillende DNA technieken om resistentiegenen aan te tonen in verschillende bacteriële ziekteverwekkers. In tegenstelling tot conventionele technieken (kweekmethoden), is men met behulp van deze DNA technieken in staat om meer betrouwbare resultaten te genereren in minder tijd. Hierdoor is het mogelijk om multi-resistente bacteriën eerder te detecteren, waardoor verdere verspreiding kan worden voorkomen doordat er eerder  de nodige maatregelen voor infectiepreventie getroffen kunnen worden. Daarnaast hebben de DNA technieken de meerwaarde dat men direct kan zien om welk soort resistentie het gaat, wat van belang is vanuit een epidemiologisch oogpunt.

Trefwoorden:

DNA techniek, resistentiegenen, bacteriële ziekteverwekkers

“Multi-scale brain connectivity with diffusion MRI”

Voor dit proefschrift werden data, verkregen uit diffusie-gewogen beeldvorming (diffusion-weighted imaging), geanalyseerd om de anatomische connectiviteit van de hersenen zowel non-invasief als in vivo te bestuderen. Het belangrijkste doel van dit onderzoek was om zowel de micro- als de macroscopische informatie te combineren die kan worden verkregen via diffusiebeeldvorming, om zo een betrouwbaar model te reconstrueren van de organisatie van de witte stof in de hersenen op micro- en macrostructureel niveau. Recente ontwikkelingen hebben aangetoond dat het via diffusiebeeldvorming mogelijk is om niet alleen de macroscopische organisatie van witte stof te achterhalen, maar ook de microscopische eigenschappen ervan, zoals axonale diameters. Hiermee kunnen modellen van hersenconnectiviteit en de vroege diagnose van bepaalde neurologische aandoeningen nog verder worden verbeterd.

Trefwoorden:

hersenen, neuroimaging, difussion imaging, witte stof

“Common standards via the backdoor; the domestic impact of asylum policy coordination in the European Union”

“The neural and psychological mechanisms of yoga and mindfulness meditation”

In dit proefschrift werd onderzocht welke neurale mechanismen ten grondslag liggen aan yoga en mindfulness meditatie. Deze mechanismen werden onder andere onderzocht met betrekking tot pijnverwerking en veroudering.  Een functionele MRI (fMRI) studie liet zien dat ervaren mediterenden tijdens een staat van mindfulness pijn niet minder sterk maar wel als minder onaangenaam ervaren. Dit komt door een uniek mechanisme van verhoogde activiteit in sensorische en een verminderde in cognitief- regulerende hersengebieden. Een fMRI studie onder ouderen toonde dat de globale, functionele hersennetwerken van beoefenaars van yoga en mindfulness meditatie efficiënter en robuuster georganiseerd waren dan die van controle personen. Mindfulness was positief gecorreleerd met zowel intelligentie als ook netwerkintegratie en netwerkbestendigheid, en lijkt daarmee een rol te spelen in het behouden van cognitie en breinfunctie. 

Trefwoorden:

hersenen, yoga, mindfulness meditatie

“The daunting complexity of cancer: Understanding the battlefield is a step towards winning the war”

“From Simple Choice to Social Decisions; on the neuro-biological and evolutionary roots of decision making”

Het onderzoek in dit proefschrift gaat over menselijke besluitvorming en pogingen om het scala aan keuzesituaties te begrijpen van eenvoudige keuzes, zoals kiezen tussen een appel en een sinaasappel, tot complexe sociale beslissingen, zoals een vreemdeling in nood helpen of de beslissing om samen te werken met een groep mensen. Er worden twee methoden uit de menselijke neurologie gebruikt, functionele hersenbeeldvorming en transcraniële magnetische stimulatie, om keuzegedrag te verbinden aan de onderliggende hersenmechanismen. Met deze technieken onderzoeken we hoe ons brein keuzeopties in zeer verschillende domeinen vergelijkt en hoe egoïsme en eerlijkheid beslissingen beïnvloeden in een sociale context. 

“Regulating the Invisible; A critical analysis of the EU’s Approach to Nanotechnologies”

Deze studie onderzoekt de rol van 'wetgeving' bij de opkomst van nanotechnologieën, die, zoals dit proefschrift beargumenteert, dienen als een volmacht voor bredere maatschappelijke veranderingen die kunnen worden geschaard onder de noemers globalisatie, functionele differentiatie van de maatschappij in bepaalde rationaliteiten en alomtegenwoordigheid van door de mens gecreëerde risico's. Het proefschrift analyseert met name door wie en hoe beslissingen worden genomen op EU-niveau gebaseerd op de EU-visie op regulering van nanotechnologie in de voedselsector en chemische sector. Dit onderzoek toont aan dat de Europese Unie haar toevlucht zoekt tot haar uitvoerende macht, onder meer door 'zachte wetgeving' zoals adviesdocumenten door EU-agentschappen of comitémaatregelen van de Commissie. Politieke beslissingen rondom de vraag 'hoe veilig is veilig genoeg?' worden dan ook doorgeschoven naar een gedepolitiseerde administratieve setting – naar 'experts' in EU-agentschappen of de Commissie. Daarmee worden de wetgevende macht en fundamentele democratische controlemechanismen van de EU gepasseerd.

Trefwoorden:

nanotechnologie, EU

“Growth Dynamics and Development: Essays in applied Econometrics and Political Economy”

Wat is de invloed van politieke instellingen op economische crises? En in hoeverre reageert armoede op wijzigingen in het gemiddelde inkomen en de verdeling ervan? In dit proefschrift worden deze vragen beantwoord in twee delen. In deel één wordt aangetoond dat negatieve regimeveranderingen van invloed zijn op het ontstaan van economische crises en wordt een theorie beschreven die illustreert hoe de duur van economische neergang afhankelijk is van de kracht van politieke instellingen en etnische heterogeniteit. In deel twee wordt gekeken naar groei, verdeling en armoede. Er wordt een nieuw empirisch kader omschreven voor het analyseren van de snelheid van armoedevermindering en dit kader wordt ook toegepast bij het onderzoeken van een belangrijk politiek vraagstuk, namelijk: zal extreme armoede in 2030 verdwenen zijn? In deel twee wordt aangetoond dat de snelheid van armoedevermindering zal vertragen. Een optimistisch scenario suggereert een armoedecijfer van 8-9 procent, ver beneden de nieuwe doelstelling van de Wereldbank van 3 procent.

Trefwoorden:

economische crisis, politiek, armoede

“Neural coding of speech and language: fMRI and EEG studies”

“Work-Family Reconciliation and Use of Parental Leave In Luxembourg; Empirical Analysis of Administrative Records”

“Biomarkers in heart failure: towards individualized therapy”This dissertation describes several biomarkers – measurable substances in the blood – that may contribute to the development of improved methods to treat heart failure. Several biomarkers can improve risk assessment for both acute and chronic heart failure. The ability to better assess the risks can help distinguish the ‘sicker’ patients from the ‘less sick’ patients. This, in turn, can help doctors determine which patients require the most intensive care. The dissertation also explores how the biomarker NT-proBNP can contribute to more individualised therapy for heart failure. The results of this study show that this strategy is not only effective in preventing hospitalisations and deaths, it is also a safe and cost-effective method that does not have additional side effects. There are new markers on the horizon that may improve this strategy further.

Key words:

heart failure, biomarkers, treatment

“Engaging with risks; citizens, science and policy in mobile phone mast siting controversies”

In the past, Dutch and Flemish citizens have protested the placement of mobile phone masts. The debate often centred on whether people can get sick from the radiation these masts emit. Following extensive research in six municipalities, Marijke Hermans suggests that focusing on health risks may mask other important concerns, such as lack of involvement and visual pollution. The focus on health may have placed the issue too firmly in the realm of science, with polarisation as a result. Science itself is becoming part of the public arena, but citizens are falling to the wayside. They are not fundamentally against the placement of phone masts, they simply want more input. They also want scientific uncertainties to be taken into account, instead of being swept under the carpet.

Key words:

mobile phone masts, science, policy, unknown risks 

“VNS in children; more than just seizure reduction”

This dissertation aims to gain more insight into the effects of vagus nerve stimulation (VNS) in children with hard-to-treat epilepsy. VNS appears to be both a tolerable and safe form of treatment.
Predictors of a favourable outcome with VNS therapy were missing at the time of this study, but research has revealed that lower baseline plasma levels of interleukin-6 is associated with a greater reduction in seizure frequency with VNS. This therefore appears to be a favourable prognostic factor. The effect of VNS on epileptic seizures could be partly explained by the way VNS influences the degradation of tryptophan, a neurotransmitter involved in mood regulation, among other things. An improvement in mood was especially seen after a prolonged period of therapeutic stimulation, independent of improved seizure control. Finally, VNS was not found to have a negative effect on behaviour or cognition.

Key words:

epilepsy, treatment, VNS

“Intracellular traffic jam: cholesterol accumulation as cause for chronic inflammatory diseases”

 A rise in obesity has brought with it a rise in the incidences of fatty liver disease. Some people go on to develop liver inflammation, or non-alcoholic hepatic steatosis (NASH), which can lead to severe liver failure or liver cancer and is currently untreatable. This dissertation explores the mechanisms that cause liver inflammation. It appears that an accumulation of cholesterol in the lysosomes (waste disposal system) of Kupffer cells is linked to a heightened inflammatory response. An effective method to treat this lysosomal cholesterol accumulation was recently discovered. This study could therefore contribute to the development of specific therapies to prevent fat accumulation in the macrophages and therefore prevent liver inflammation.  

Key words:

hepatitis, steatosis, macrophages

“Annexin A1 and annexin A5 in cardiovascular disease”

This study involves two members of the annexin family of proteins and their relationship to cardiovascular disease. The main findings are the inhibiting effect of annexin A5 on clearing away dead cells and, therefore, the enhancing effect on ‘arteriosclerosis’. Annexin A1 has an anti-inflammatory effect and was successful in the treatment of ‘arteriosclerosis’ as well as the reduction of damage following myocardial infarction. These findings may lead to the development of new drugs.

Key words:

cardiovascular disease, proteins, arteriosclerosis

“Application of omics to immunotoxicology: from Mechanisms of action to alternative testing strategies”

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Key words:

immunotoxicology, testing strategies

“Internal R&D, external R&D, and firm innovation evidence from the pharmaceutical industry”

“Effects of plant sterol and stanol esters on oxyphytosterol concentrations and postprandial metabolism”

Sterols and stanols are components of plants that are added to functional foods, such as enriched margarine, with the aim of lowering ‘bad’ LDL cholesterol. This dissertation investigates whether consuming enriched margarine also affects oxyphytosterol concentrations (oxidised plant sterols) during fasting and after a meal. Oxyphytosterol concentrations may play a role in the development of cardiovascular disease. This dissertation also examines the effects of two types of antioxidants on oxyphytosterol concentrations. Higher oxyphytosterol concentrations were found in diabetics than in non-diabetics and while the ingestion of plant sterols and antioxidants had no effect on these concentrations, the ingestion of plant stanols did generate a reduction of certain oxyphytosterol concentrations. After eating a meal enriched with plant sterols, higher oxyphytosterol concentrations were found in subjects after they consumed a second meal. It is not yet clear whether oxyphytosterol concentrations are derived from food or whether they are formed in the body.

Key words: 

nutrition, plant sterols, plant stanols, oxyphytosterol concentrations 

“Option Markets: Implied information, Equity process and Risk Management”

“Towards proactive care for potentially frail older people in general practice”

Ensuring that the elderly can live independently at home for as long as possible is central to Dutch healthcare policy. This is pursued by [G]OUD, Gezond Oud in Limburg (Healthy Ageing in Limburg). By making preventative home visits to people over the age of 75, general practitioners can identify vulnerability at an early stage and arrange for the right support in terms of healthcare and wellbeing. This dissertation describes the development, the practical feasibility, and the effectiveness of [G]OUD. Despite the enthusiastic response from GP practices and elderly people, this approach has yet to make a demonstrable impact on quality of life or on the self-reliance of elderly people. This can be attributed to, among other things, the high level of care in the Netherlands and the fact that most of the research participants were relatively healthy. As a result, the study did not assess the intended target group: vulnerable elderly people. More attention is needed in order to better align and coordinate elderly care.

Key words:

elderly care, vulnerability, early detection, primary care

“Cellular immunotherapy; from stem cell to lymphocyte”

To reduce the mortality rate in cancer patients who undergo stem cell transplantation, a study was conducted on the development of cellular immunotherapy using immature T-cells to strengthen the immune system after treatment. A clinically applicable system was developed for producing these cells from stem cells. It was found that vitamin C significantly improved production and brought about greater cell yield for therapeutic purposes. It was also found that patients with haematological malignancy (i.e. certain forms of cancer, including leukaemia) had lower vitamin C levels. Administering vitamin C may therefore promote immune recovery.

Key words:

immune system, stem cell transplantation, immunotherapy, vitamin C

“National Parliaments in the Aftermath of the Lisbon Treaty; Adaptation to the ‘New Opportunity Structure’”

This dissertation examines the influence of European integration on national parliaments. The Treaty of Lisbon granted national parliaments new responsibilities in terms of European affairs. This, in turn, changed the relationship between various parliamentary players, namely parliament members, parliamentary committees, and employees of parliamentary administrations. One of the views argued in this dissertation is that parliaments focus primarily on the distribution of tasks between member states and the EU. Much less attention is paid to the content of European legislation, which can have a negative impact on the decision-making process and the national debate surrounding issues of European importance.

Key words:

European integration, national parliament

“Considerations in designing an adult hearing screening programme”

“Urban Water Management Reform: the case of China”

Water scarcity is particularly acute in urban areas in developing countries, where a safe and secure water supply is threatened by rapid economic development and urbanization, population growth, and the deterioration of water environment. In this dissertation, it is argued that the appropriate policy interventions might allow developing countries to achieve economic development with less capita water consumptions, the privatization reform and the participation of multinational corporations in Chinese water sector contributed to the growth of productivity of the whole sector, and environmental campaign and public participation enhance citizens’ environmental awareness which in turn contribute to water conservation.

Key words:

China, water management

“Health technology assessment in osteoporosis: New perspectives from adherence and preference studies”

“Realities and illusions of human migration: a geographical perspective”

“Branch-and-cut algorithms for graph problems”

“Obtaining information from eyewitnesses: Effects of retrieval support in eyewitness interviews”

In many police cases eyewitness statements are the only available evidence. Hence, whether a crime can be solved may critically depend on the statement quality. Seeking to improve the reliability of eyewitness statements, the thesis examined the effectiveness of retrieval support during the interview when the witnessing conditions were suboptimal (e.g., experience of stress during the crime), as well as retrieval support through repeated interviews. Retrieval support refers to techniques that help witnesses get access to their recollections (e.g., asking the witness to picture the incident in his/her mind). The results showed that retrieval support improves recall performance only after some suboptimal conditions. Furthermore, recall performance can be enhanced when witnesses are interviewed several times. Unfortunately, police detectives in the Netherlands are not aware of the latter, as this research has shown. Therefore, interview trainings need to be revised to improve police detectives’ knowledge about human memory.

Key words:

interviewing; eyewitness memory; eyewitness testimony; retrieval support; police

“In vitro culture of human embryos; effects on fetal development and the role of the placenta”

IVF children are at a slight developmental disadvantage compared to children who were conceived naturally. The cause of low birth weight and premature birth remains unknown. The effects in human babies are less pronounced than in animals and, while IVF newborns may appear perfectly normal at birth, they could go on to develop problems later in life. This study shows that culturing human embryos for two to three days in two different culture mediums results in a significant difference in birth weight after nine months. A difference in fetal development was also noted. Changes were found in the placentas of women who had undergone IVF treatment that were not found in women who had conceived naturally. It is therefore important that manufacturers of IVF cultures publish the exact composition of their mediums. Additionally, the safety of IVF warrants further research.

Key words:

IVF, risks, culture medium, placenta

“The Maternal Brain in Pregnancy and Preeclampsia”

“Een arbeidersbuurt onder de rook van ‘De Sphinx’ Het Boschstraatkwartier-Oost te Maastricht. Een sociaal-ruimtelijke geschiedenis, 1829-1904”

In 1834, Petrus Regout laid the foundations for his glass and ceramics empire, which would later become NV De Sphinx. This study explores the socio-spatial effects of the rise of the ceramics industry on the Boschstraatkwartier-Oost, a district in the shadow of the Regout & Co. factories. Seventy-five years after these factories were founded, the socio-demographically diverse district had become an overcrowded slum where slumlords thrived at the expense of the Sphinx employees, popularly known as pottemennekes. Children grew up in appalling conditions and started working in the factories at an early age, even after the ban on child labour was introduced in 1874. In the fifties, sociologists began studying the ‘unsocial families’ living in this disadvantaged area. However, a life-cycle assessment of five generations of families living in the Boschstraatkwartier district revealed far greater variation and subtleties in this community than the sociologists originally assumed.

Key words:

Maastricht, history, De Sphinx

“COPD and comorbidity”

This thesis focuses on the prevalence and impact of simultaneously existing disorders or comorbid conditions in COPD patients. Common comorbid conditions in COPD patients were detected systematically. Electrocardiography showed a high prevalence of heart damage, which is associated with poorer outcome. Other comorbid conditions such as high blood sugar levels, obesity, high blood pressure, osteoporosis, anxiety and depression were found to be common as well. Comorbidity is present in almost all COPD patients and at least four simultaneously occurring comorbid conditions are present in over 50% of the patients. Patterns could be recognised and patients could be divided into five groups based on these comorbid conditions. In conclusion, it was shown that neither separate comorbid conditions nor comorbidity clusters prevent pulmonary rehabilitation from being effective in COPD patients. 

Key words:

COPD, comorbid conditions

“The Impact of Brands on Innovation and Firm Performance – Empirical Evidence from Germany” 

Merken behoren tot de meest waardevolle immateriële activa die een bedrijf kan hebben. Een gevestigd merk genereert niet alleen bekendheid en aandacht voor de merkproducten van een bedrijf, maar draagt ook bij aan de reputatie, geloofwaardigheid en andere gunstige associaties. Het onderzoek dat in dit proefschrift wordt gepresenteerd, beschrijft de impact van merken op innovatie en bedrijfsprestaties. De empirische analyse toont aan dat bedrijven de kans op commercieel succes van hun productinnovaties kunnen vergroten door een merk te gebruiken. Het proefschrift toont ook via een representatieve steekproef onder Duitse bedrijven aan dat eerdere merkgerelateerde investeringen bijdragen aan huidige winsten en dat merken en andere immateriële activa worden geässocieerd met hogere productiviteit.

Trefwoorden:

merk, innovatie, bedrijfsprestaties

“Cyclic nucleotide signaling a nd synaptic plasticity”

“Dosimetry of preclinical and clinical case studies of 18F-radiopharmaceuticals using Positron Emission Tomography and Computed Tomography: Methods of quantification, their improvement and considerations of critical exposures”

Bij computertomografie (CT) en positronemissietomografie (PET) wordt gebruikgemaakt van ioniserende straling. Deze technieken worden veelvuldig gebruikt in preklinische en klinische fases. De mate waarin dieren en mensen worden blootgesteld aan straling dient nader te worden bekeken. 
In dit proefschrift is de stralingsdosimetrie van 18F-radiofarmaceutica  onderzocht bij mensen en dieren en er wordt een meer ethische en economische benadering van preklinische dosimetrie gepresenteerd. Er is ook gekeken naar de dosimetrie van de microCT eXplore 120.
Dieren zijn blootgesteld aan significante hoeveelheden straling in longitudinale onderzoeken naar zowel PET als CT, die onderzoekers in acht dienen te nemen. De onderzochte 18F-radiofarmaceutica werden wat de straling betreft als veilig beschouwd voor gebruik bij mensen.

Trefwoorden:

straling, CT, PET, radiofarmaceutica

“Behavioral activation for depressed patients in Iran: Effectiveness, predictors and mediators in the context of a Randomized trial”

Gedragsactivatie is een relatief nieuwe psychologische behandeling die een bruikbaar alternatief en effectieve behandeling kan zijn voor mensen met een ernstige depressieve stoornis. De bevindingen van dit proefschrift tonen dat de deelnemers die de voorkeur gaven aan psychologische behandeling tegen depressie, meer profijt zouden kunnen hebben van gedragsactivatie dan van antidepressiva. De uitval van de behandeling was hoger voor de groep die de voorkeur gaf aan psychologische behandeling, maar tegelijkertijd antidepressiva kregen. Het implementeren van gedragsactivatie in klinische settings is eenvoudiger dan cognitieve gedragstherapie. Deze methode kan na een kortstondige training worden gegeven door GGZ-professionals. Behandeling door middel van gedragsactivatie kan een zeer kosteneffectieve interventie voor depressie zijn.

Trefwoorden:

Gedragsactivatie, depressie, behandeling, Iran

“The big challenge of small sentinel lymph node tumor Burden in breast cancer”

“Strategies to activate brown adipose tissue in humans”

Het is bekend dat wit vetweefsel energie opslaat in de vorm van vet. Het bruine vet kan juist vetten en suikers verbranden voor productie van warmte in het lichaam. In de kou wordt de activatie van bruin vet gestimuleerd. Dat stimuleren van bruin vet kan mogelijk ingezet worden voor gewichtsregulatie. Naast kou zijn in dit proefschrift alternatieve manieren om bruin vet te stimuleren onderzocht. Uit de studies blijkt dat blootstelling aan koude de meest effectieve manier is om bruin vet te activeren. Daarnaast blijkt dat bruin vet ook actief is na de inname van een calorierijke maaltijd. Bruin vet kan dus mogelijk op verschillende manieren een rol spelen in het reguleren van een gezonde energiebalans.

Trefwoorden:

bruin vet, gewichtsregulatie

“Molecular biology of the Birt-Hogg-Dubé syndrome”

Het Birt-Hogg-Dubé (BHD) syndroom is een erfelijke, zeldzame ziekte waarbij patiënten goedaardige huidtumoren, cystes in verschillende organen, klaplongen en niertumoren kunnen ontwikkelen. Omdat deze symptomen ook voorkomen in de bredere populatie is inzicht in de ontstaansmechanismes hiervan belangrijk voor het verbeteren van behandelingen. BHD wordt veroorzaakt door een fout in het eiwit folliculin (FLCN). Dit proefschrift toont aan dat verlies van normaal FLCN leidt tot vertraging van de aanmaak van het cilium, een antenne-achtige structuur op de cel, en tot een verhoogde activiteit van een signaalroute die betrokken is bij de aanpassing van cellen bij verminderde zuurstof. Verder is het recycling systeem dat oude onderdelen van de cel afbreekt geremd.

Trefwoorden:

Birt-Hogg-Dubé syndroom, ontstaansmechanisme

“Thiopurines in inflammatory Bowel Diseases”

Aan patiënten met de ziekte van Crohn en colitis ulcerosa worden vaak thiopurines als onderhoudsbehandeling (azathioprine en 6-mercaptopurine) voorgeschreven. 
Bij de afbraak van thiopurines ontstaan 6-TGN, die van belang zijn voor het therapeutisch effect, maar ook schadelijk kunnen zijn voor de witte bloedcellen, en de 6-MMPR metabolieten die veelal leiden tot het vroegtijdig staken van de behandeling door het optreden van leverschade en vervelende bijwerkingen, zoals misselijkheid en braken. 
Dit proefschrift beschrijft een onderzoek naar het nut van het meten van deze afbraakproducten. Het meten van deze afbraakproducten na één week van de behandeling voorspelt het optreden van deze bijwerkingen. Er blijkt dat er vaak sprake is van een te lage dosering en verder is één op de zes patiënten therapie-ontrouw. 
De meting van afbraakproducten biedt belangrijke mogelijkheden ter verbetering van de effectiviteit en veiligheid van thiopurines.

Trefwoorden:

ziekte van Crohn, colitis ulcerosa, behandeling, thiopurines, afbraakproducten

“The quality of vocational education. Differing values, behavior and policy”

In dit proefschrift wordt met een vignetstudie in beeld gebracht dat de betrokkenen bij het beroepsonderwijs verschillende accenten leggen bij de kwaliteit van een beroepsopleiding. Beleidsmakers vinden het belangrijk dat er voldoende diploma’s gehaald worden, studenten dat ze  goede docenten hebben, docenten dat de opleiding structuur biedt en werkplekbegeleiders dat het curriculum uitdagend is. Er is echter een aspect dat iedereen belangrijk vindt: dat werkgevers tevreden zijn over afgestudeerde studenten. Vervolgens is  bij studenten gekeken of hun kwaliteitsidee ook terug komt in hun studiekeuze en wat de overheid doet om de kwaliteit van het beroepsonderwijs te stimuleren.   Door inzicht in de meningen en het gedrag van betrokkenen kan de overheid beter reflecteren op haar beleid, dit gerichter inzetten en daar waar mogelijk ruimte laten aan het onderwijsveld om het onderwijs in te richten naar eigen inzicht.

Trefwoorden:

onderwijskwaliteit, beroepsonderwijs, mbo, vignetstudie, onderwijsbeleid, schoolkeuze

“What’s in a Team: a dynamic perspective on Intragroup Conflict and Team Turnover”

Dit proefschrift richt zich op groepsprocessen die de prestaties van teams kunnen beïnvloeden en dan met name op conflicten die zich kunnen voordoen binnen een team, diversiteit in teams en veranderingen in de teamsamenstelling (teamverloop). Het onderzoek is uitgevoerd over een periode van 4 jaar binnen een zorginstelling voor mensen met een (verstandelijke) beperking. 
Dit proefschrift introduceert een aangepaste manier om teamverloop te meten. Traditioneel gezien wordt teamverloop alleen kwantitatief gemeten. Hier wordt deze uitgebreid met een kwalitatieve component, gebaseerd op de competenties van de medewerkers. 
De resultaten van dit proefschrift laten zien dat teamverloop tot taak-gerelateerde conflicten kan leiden, en dat daarmee de teamprestaties negatief kunnen worden beïnvloed. Alleen in teams met ervaren medewerkers leidt teamverloop niet tot conflicten en is daar dan ook niet van invloed op de prestatie.

Trefwoorden:

teams, groepsprocessen, prestaties

“A good laugh and a long sleep; Insights from prospective and ambulatory assessments about the importance of positive affect and sleep in mental health”

Dit proefschrift focust op het gebruik van de Experience-Sampling-Methode (ESM) in geestelijke gezondheids- en slaaponderzoek. ESM is een dagboektechniek die in het dagelijks leven stemmingen, ervaringen en gedrag, prospectief meet. ESM werd gebruikt om de link tussen slaap, stemming en depressie te onderzoeken. Het bleek dat een waargenomen slechtere slaapkwaliteit samenhangt met minder positieve stemming de volgende dag en met verhoogde depressieve klachten op de lange termijn. Voorts werd ESM voor het eerst succesvol als therapeutische toepassing gebruikt. Informatie over stemming en gedrag, die depressieve patiënten in ket kader van een ESM-onderzoek elektronisch hebben verzameld, werd teruggekoppeld om meer inzicht te geven.

Trefwoorden:

Experience-Sampling-Methode (ESM), depressie, onderzoek, therapie

“Higher education in the national and international economy”

“Exercise strategies to optimize glycemic control in type 2 diabetes”

“Frailty in old age; conceptualization and care innovations”

Dit proefschrift gaat in op aspecten rondom conceptualisering van het begrip kwetsbaarheid. Tevens wordt ingegaan op enkele zorgvernieuwingen in intra- en extramurale setting. Wat betreft het begrip kwetsbaarheid is een van de conclusies dat kwetsbaarheid als zodanig wellicht te complex is om te vatten in een korte, simpele en snel af te nemen vragenlijst. Mogelijk is het meer zinvol na te gaan voor welke specifieke uitkomsten ouderen kwetsbaar zijn of een verhoogd risico hebben dan een algemene conclusie te trekken of ouderen wel of niet kwetsbaar zijn. De drie beschreven zorgvernieuwingen laten zien dat de ontwikkeling van adequate zorginnovaties om dagelijks functioneren van kwetsbare ouderen verder te verbeteren een uitdaging blijft. Het lijkt zinvoller om de bestaande zorg, die al van hoog niveau is, op meer efficiënte wijze in te richten.

Trefwoorden:

kwetsbaarheid, ouderenzorg, zorgvernieuwingen, public health

“Biological Data in Pathways and Networks”

In de vele cellen in ons lichaam werken genen, proteïnen en metabolieten samen. Zodra er iets in dit complexe netwerk verkeerd gaat, kunnen er ziektes optreden. In de groeiende nieuwe onderzoeksdiscipline genaamd systeembiologie proberen we een beter begrip te verkrijgen van de werking van cellen bij gezondheid en ziekte. In dit proefschrift worden nieuwe instrumenten gepresenteerd die de verbindingen tussen proteïnen onderling en hun invloed op het functioneren en het gedrag van cellen organiseren, visualiseren en analyseren. Aan de hand van voeding- en obesitas studies wordt gedemonstreerd hoe deze nieuwe instrumenten tot een beter begrip leiden van de samenhang van deze processen en hoe deze beïnvloed kunnen worden door verschillende medicijnen en voedingsmiddelen. Dit biedt aanknopingspunten voor beter gecombineerde behandelingen en gezondere diëten.

Trefwoorden:

Systeembiologie, netwerken, voeding

“Exploring course and outcome across the psychosis-continuum”

“Economic preferences and financial risktaking”

“Dopayours is not dopamine: genetic, environmental and pathological variations in dopaminergic stress processing”

Overmatige blootstelling aan stress is één van de gevaren van deze moderne tijd. Wat er in de hersenen gebeurt tijdens stress is echter niet duidelijk. Dit proefschrift richt zich op het meten van de effecten van stress op dopaminerge neurotransmissie in het brein. Mensen werden blootgesteld aan experimentele stress (een moeilijke rekentaak) en dagelijks leven stress werd gemeten. De belangrijkste conclusie was dat lage dopamine niveaus in het brein tijdens stress een verhoogde stress-gevoeligheid en psychische klachten naar aanleiding van stress voorspelden. Hoge dopamine niveaus werkten beschermend voor stress. Deze kennis kan bijdragen aan de ontwikkeling van farmacologische interventies voor stress-gerelateerde psychische klachten.

Trefwoorden:

stress, dopamine, PET, beeldvorming, psychiatrie 

“Dietary proteins and blood pressure regulation”

Een eiwitrijk voedingspatroon kan de bloeddruk verbeteren. Het is nog onduidelijk of dat door de eiwitten zelf komt en welke eiwitrijke voedingsbronnen het beste effect hebben. In dit proefschrift werd onderzocht of dagelijkse consumptie van een mengsel van gezuiverde dierlijke en plantaardige eiwitten in plaats van koolhydraten (glucose) invloed had op de bloeddruk van mensen met overgewicht en een licht verhoogde bloeddruk.  Het dagelijks vervangen van 60 gram koolhydraten in de voeding voor 60 gram van het eiwitmengsel verlaagde de bloeddruk na 4 weken. Een verbeterde vaatfunctie zou hier een rol bij kunnen spelen. Echter, observaties van de bloeddruk en vaatfunctie direct na eiwitinname bevestigen dit beeld niet en laten juist een grotere bloeddrukdaling na koolhydraatinname zien zonder verschillen in vaatfunctie. Een mogelijke verklaring is dat eiwitten en koolhydraten direct na inname verschillende hormonale effecten teweegbrengen, waardoor de bloeddrukreactie verschilt van het effect dat op lange termijn wordt waargenomen.

Trefwoorden:

bloeddruk, voeding, eiwitten, koolhydraten

“The adaptation process after acquired brain injury: Pieces of the puzzle”

Dit proefschrift toont dat een lage zelf-effectiviteit en in hoge mate gebruik maken van emotiegerichte coping (het uiten van negatieve emoties) in de subacute fase na doormaken van hersenletsel, voorspellend zijn voor een slechtere kwaliteit van leven op de langere termijn. Het is dus belangrijk om in een vroeg stadium deze factoren te screenen om patiënten met een hoger risico op een slechtere uitkomst te identificeren. Verder blijkt ook dat patiënten met een hogere mate van zelf-effectiviteit succesvoller zijn in het bereiken van hun belangrijke levensdoelen en daarmee een hogere kwaliteit van leven ervaren, minder stress hebben en actievere vormen van coping hanteren.

Trefwoorden:

hersenletsel, zelf-effectiviteit, coping, kwaliteit van leven

“Public health and international health educational programmes for low- and middle-income countries: questioning their outcomes and impact”

“Basic Mathematics Skills Development in Children: an evaluative study on cognitive and educational factors”

In Nederland ligt de rekenontwikkeling van kinderen lager dan verwacht. Er is dan ook veel belangstelling voor hoe deze verbeterd kan worden. De resultaten van dit proefschrift duiden op het belang van de vaardigheid om de waarde van een getal snel en juist te kunnen verwerken. Deze vaardigheid kan bij groep 2-leerlingen gebruikt worden als een vroege voorspeller van mogelijke rekenproblemen. Het is belangrijk dat leerlingen al in groep 1 en 2 vertrouwd raken met getallen en hun waarden. Ook zien we dat een jaar extra onderwijs alleen effectief is voor het verbeteren van basis reken-wiskunde vaardigheden bij groep 2-leerlingen. Dit is het gevolg van een disbalans tussen het aanleren van wiskundige redeneervaardigheden en het systematisch oefenen van basis reken-wiskunde vaardigheden. Een laatste beleidsimplicatie is dat interventies (b.v. educatieve computerprogramma’s) toegesneden moeten worden op de cognitieve sterke en zwakke punten en al aanwezige reken-wiskunde vaardigheden van leerlingen.

Trefwoorden:

basisonderwijs, rekenontwikkeling, beleid

“Stem and Progenitor Cells in Preterm Infants: Role in the Pathogenesis and Potential for Therapy”

“Urinary and salivary S100B monitoring in high risk infants”

“AFFECT DYNAMICS; A focus on genes, stress, and an opportunity for change”

“Daily physical activity and COPD“

“Surving childhood new perspectives on the link between childhood trauma and psychosis”

“Audit Committee Design and Effectiveness”

“Polyols and polyphenols against glucotoxicity”

This thesis shows that certain food substances can have therapeutic implications for patients suffering from diabetes. One of the substances we studied is erythritol, a naturally-occurring substance which is present in small amounts in some fruits as well as beer and wine. It is shown that erythritol protects blood vessel cells (the lining of our vascular system) and beta cells (cells which produce insulin) against harmful effects of glucose. The substances we studied often had several small effects which together produced a large positive effect on cells. This is beneficial in the management of chronic diseases, because a ‘gentle’ approach is preferable to a ‘harsh’ approach in which a blow is struck, as is often the case with drugs.

Key words:

diabetes, food substances, protective effect

“Inside out; On stereotype awareness, childhood trauma and stigma in psychosis”

This thesis examines the factors in a person’s environment that can play a role in psychotic disorders: stigmatisation and trauma. It looks at data from the GROUP study on the degree to which people are aware of negative, generalised convictions (stereotyping) about people with psychiatric disorders and their families. A higher degree of self-worth is associated with less awareness of stereotyping of people with psychoses. More childhood trauma is associated with more awareness of stereotyping. This thesis contributes towards our knowledge about what makes people vulnerable or non-vulnerable to stigmatisation and provides guidelines for training in clinical practice.

Key words:

stigmatisation, stereotyping, childhood trauma and psychosis

“Extended Psychosis Phenotype  in the wider Social Environment”

In this thesis, psychosis is considered in an extended phenotype including non-clinical experiences without distress or impairment, psychotic experiences with mild to moderate distress but without impairment and help seeking, and full-blown psychotic disorder. An unique methodology to psychometrically measure and to evaluate the whole spectrum is used. One in four individuals in the general population sample at least once experienced a delusional type of thinking or a hallucination. Due to psychotic experiences, a significant proportion of individuals displayed distress, impairment and help-seeking in various forms, and some of them became long-time service users. Risk factors such as cannabis use and familial liability led to disproportionate shift in the severity of the psychosis phenotype. Furthermore, associations between proxy genetic factors and the extended psychosis phenotype were moderated by contextual factors within wider social environment including neighbourhood-level social disadvantage and social capital.

Key words:

Psychosis, continuum, urban environment, social capital, social disadvantage

“Validity and diagnostic value of tests used in thediagnostic work up of haemostatic disorders!”

Medical decisions on diagnosis and treatment depend on laboratory, imaging and other tests, which must be accurate and precise to be of clinical value. Premature application may lead to wrong diagnosis, unnecessary delays in starting appropriate treatment, or even hazardous therapy. We identified major problems in precision and accuracy of tests used in the work-up of patients with a bleeding tendency and thromboembolic disorders. Our results call for concerted efforts to ensure appropriate evaluation studies. The needs we identified may promote a large number of studies, which may bring the development of medical tests further, and subsequently improve patient care.

Key words:

medical tests, evaluation studies, bleeding disor-ders, venous thromboembolism

“Rectal cancer imaging; How about the nodes?”

“Giving maltreated children a voice”

“Stepping Stone Cities?; exploring Urban Greening and Gardening as a Viable Contribution to Global Biodiversity Conservation”

Is the greening of cities a way to contribute to protecting global biodiversity? This question has been researched by looking at worldviews behind nature conservation strategies and organisations and by looking at the public support for urban greenery. Traditional conservation organisations should focus their sights more on the nature in and around cities. This could help increase residents’ practical knowledge of nature. There is a growing focus on collectively making cities greener, but private individuals are choosing more for stones than for biodiversity in their own gardens. There is a lot to be gained in this area. A focus on ‘new’ urban nature, however, can never compensate for the conservation of the ‘old’ wild nature.

Key words:

urban nature; biodiversity; gardening; conservation

“MOVING TEAMS FORWARD; Effects of feedback and team reflexivity on team performance”

Why do smart teams move backwards? Teams can be loaded with exceptionally smart professionals, but may get heavily frustrated because they failed to achieve their objectives or improve their performance. Coordination and reflection seem to explain why some teams move forward while others don't progress.  Prevention of downward spirals in performance is essential to help teams. This research shows that engaging in essential team behaviors such as sharing and building knowledge and reflecting on team functioning will drive them to success. Additionally, it demonstrates that teams can gain substantially when they are provided with accurate and timely feedback and opportunities for guided reflection on why things went right or wrong.

Key words:

team performance, team learning behavior, feedback

“OCD matters in psychosis”

Obsessive-compulsive disorder (OCD) and psychosis co-occur far more often than expected, but the causes and consequences of this remain unclear. This research shows that even before the emergence of a diagnosable disorder, mild features of OCD and psychosis co-occur. This heightens the risk that the severity of the psychotic symptoms – and hence also the care needs – will increase. In addition, the results point to a shared familial vulnerability: brothers and sisters of patients with psychotic disorders also have more obsessive-compulsive symptoms. In practice, people with combined obsessive-compulsive and psychotic symptoms should therefore be monitored particularly closely.

Key words:

early detection, obsessive-compulsive disorder, psychosis, schizophrenia, psychiatry, care needs

“Designing for Success: Investigating Design as a Driver for Innovation”

The success of companies such as Apple or Alessi has pointed to a positive association between companies’ foci on product design and their overall innovation performance. Therefore, the past decade has seen an increased interest among company managers in deciphering the DNA of such design-oriented companies, in order to extract their design related processes, principles and tools, and apply them to various innovation contexts. This thesis frames the overall impact of design and examines its drivers and innovation outcomes on a corporate and on a project level. The results demonstrate that the economic benefits of design efforts can only partially be traced back to tangible outputs; instead a substantial proportion of its success can be ascribed to the managerial, processes technical and cultural aspects of design transcending companies and guiding innovation projects.

Key words:

innovation management, design thinking, design-driven innovation, design orientation 

“Toxicogenomics responses in the in vitro liver; A view on human interindividual variation”

Toxicity for humans often is falsely predicted based on animal tests, possibly amongst others due to human interindividual variation. Human-based alternative screening methods are scarce. The liver, a primary site for toxicity, is a candidate for a human-based alternative model for safety screening. The aim of this study is to evaluate human interindividual variation in several liver-based in vitro cell models. The results show that these models indeed can be used to evaluate interindividual variation, especially when several research techniques are combined. Possibly these models can be used to relieve the burden on animal-testing in the future.

Key words:

Liver, toxicity, interindividual variation, alternatives to animal tests

“THE MULTIDISCIPLINARY TEAM GENODERMATOSIS: a simple strategy to solve  complex cases”

“Carotid baroreflex activation therapy. Potential mechanisms in resistant hypertension”

High blood pressure is a common health problem. Despite the many drugs available to treat it, the blood pressure of roughly 50% of patients remains too high. This not only has serious consequences for patients (such as heart attacks and strokes), but also places a heavy burden on the healthcare system. This thesis investigates a new, pacemaker-like device that stimulates blood pressure sensors in the neck. These sensors lower blood pressure via complex signals to the brain. This treatment has a safe and lasting effect on blood pressure, without exhausting the blood pressure sensors or damaging the kidneys. While further research is needed to fully clarify the underlying mechanisms, the thesis identifies a number of hormones and proteins that could play a role in this process.

Key words:

high blood pressure, pacemaker, mechanisms

“Optimism. The natural placebo. Cognitive, behavioural and motivational mechanisms of resilience towards pain”

Optimism leads to less pain! That is the main conclusion of this thesis in which the causal relationship between optimism and pain is demonstrated experimentally for the first time. The research confirms that positive future expectations are associated with fewer negative thoughts about the significance/impact of pain and with greater flexibility in dealing with life goals. In this way, a positive view of the future leads to a better wellbeing in the now. This knowledge contributes to protecting people from the negative effects of chronic pain. This is especially important because chronic pain does not always have a medical solution.

Key words:

optimism, chronic pain, positive psychology

“NOXious oxidative stress: from head to toe and back”

In many cardiovascular diseases, reactive oxygen species cause irreparable organ damage. Inhibition of NOX, an important source of such oxygen species, could be a possible treatment method. This thesis shows that certain forms of NOX play a key role after a stroke has occurred in mouse models. The inhibition of NOX4 results in less brain damage, whereas the activation of NOX5 causes more damage (the latter only goes for female mice). Furthermore, elevation of the blood pressure was observed as a result of NOX5 activation.
The effects found in this study are shown to be exclusively related to brain disease, as no effects were found in models of myocardial infarction or peripheral vascular disease.

Key words:

cardiovascular diseases, oxygen species, NOX, stroke

“In vitro assay systems in the development of therapeutic interventions strategies for neuroprotection and repair”

“Health Benefits of Epicatechin and other flavonoids”

Flavonoids are substances found in various food products. This study focusses on flavonols, a subgroup of the flavonoid family. Tea and cacao contain relatively high concentrations of one of these flavonols, epicatechin. The antioxidant and anti-inflammatory effects of epicatechin can have important implications for chronic inflammatory diseases such as rheumatoid arthritis, chronic enteritis, asthma and COPD. Our study results also show that flavonols have a positive effect on vascular health. During an eight-week period of flavonol intake from grape seeds vascular function in test subjects improved and blood markers of oxidative stress and inflammation were reduced. In addition, our findings suggest that epicachetin and other flavonoids counteract the effects of anti-inflammatory drugs. Therefore, it is conceivable that both will be prescribed simultaneously in the future.

Key words:

flavonols, epicatechin, anti-inflammatory

“Preterm birth after antenatal inflammation as underlying cause of bronchial hyperreactivity”

Preterm birth is often caused by an intrauterine infection (chorioamnionitis). As these children grow older, they more frequently develop bronchial hyperreactivity (asthmatic symptom). This thesis gives insight into how lung development and airway function were influenced by antenatal inflammation as gestation advances and during the first period after birth. For this a sheep model was used. This thesis has identified a potential link between activation of the prenatal immune status and impaired lung development, resulting in altered airway reactivity postnatal. This should provide a basis for future research towards the understanding and treating of asthma in early childhood after preterm birth.

Key words:

preterm birth, lung development, antenatal inflammation, asthma

“International Aspects of the CCCTB in Europe”

On 16 March 2011, the European Commission proposed a Council Directive on a common consolidated corporate tax base (CCCTB). The purpose of this research was to analyse specific international aspects of the CCCTB, which in the opinion of Tiiu Albin Pereira, form the necessary basis for the possible introduction of a common European corporate tax system. While the author believes that the CCCTB can function well in parallel to the current international framework of corporate tax systems, as follows from the research, some of the provisions of the proposed CCCTB Directive as well the policy behind them should be carefully reconsidered. In addition, the current research highlights the likely conflicts arising from the potential introduction of the CCCTB among a number of Member States in the future and proposes solutions.

Key words:

Corporate tax; EU tax harmonization

“Diabetes care and the introduction of a new standard in the Netherlands; A closer look from the perspectives of health care professionals and patients”

This thesis shows that the introduction of the Care Standard for diabetes (supported by the National Diabetes Action Programme) has made a positive contribution to the improvement of care given to patients suffering from diabetes in the Netherlands. The National Diabetes Action Programme has resulted in the implementation of the Care Standard for diabetes into the Dutch health care. Studies on patients suffering from diabetes show that support of autonomy and strategies designed to improve perceived patient competencies are important factors in future interventions aimed at the improvement of self-management and quality of life. In the future, an integrated multidisciplinary patient-focused approach to chronic diseases is needed.

Key words:

diabetes, implementation care standard, autonomy support

“Uitkeringen aan aandeelhouders in het nieuwe BV-recht; besluitvorming, vertegenwoordiging en vereenzelving”

“Gout, uric acid, and cardiovascular disease; know your enemy”

“Interaction of dietary protein with energy balance”

This thesis studied the effects high-protein and low-protein diets have on food intake and energy consumption. In the laboratory restaurant, test subjects had daily low-protein, normal-protein or high-protein meals, each taken for twelve days. They spontaneously ate less during high-protein meals than during low-protein and normal-protein meals. In a study which was carried out later, this satiating effect of proteins was reduced in test subjects who had high-protein or low-protein meals for twelve weeks while having to maintain their weight. The energy consumption was maintained in test subjects having high-protein meals, whereas it was reduced in test subjects having low-protein meals. Therefore, it was concluded that a high-protein diet may prevent weight gain due to its impact on satiation and food intake as well as energy consumption.

Key words:

diet, proteins, intake, energy consumption

“A cutting Culture: gender and identification in the figured world of surgery”

“The Role of Mood, Habitual Goals and Primed Goals in Painful and Non-Painful Task Persistence”

“Molecular studies of FLCN-related diseases”

Birt-Hogg-Dubé syndrome (BHD) is a rare genetic disorder in which patients are at an increased risk of developing benign facial tumours, pneumothorax and cancer of the kidneys. Understanding of the pathogenic mechanisms underlying these symptoms is necessary for improving treatment options as they also occur in the general population. This thesis examined the function of folliculin (FLCN), the protein which is damaged in BHD patients, and its interacting partner folliculin-interacting protein 1 (FNIP1). It was shown that both proteins are found in cilia, a sort of cellular antennae, and BHD symptoms are caused by a disruption of these structures. Furthermore, it was shown that both proteins play an important role in the development of the zebrafish embryo. These laboratory animal models may be used to screen drugs against BHD.

Key words:

Birt-Hogg-Dubé syndrome, cancer of the kidneys, cilia, zebrafish

“Epidural analgesia during labour: choices and consequences”

Given the fact that an increasing number of women are requesting an epidural when giving birth, it is important to examine the adverse effects associated with this. A quadrupling in the use of epidurals (on request) in the Netherlands over the last ten years has not resulted in a greater number of assisted deliveries (caesarean section or forceps delivery/vacuum-extractor assisted delivery). The probability of needing an assisted delivery is not affected by the degree of cervical dilation at the time of giving the epidural. The effect of a standard or routine epidural on the birth has never before been examined. Our study shows that routinely giving epidural results in a greater number of side effects such as low blood pressure, limited leg movement and indeed more assisted deliveries, and is therefore not recommended. 

Key words:

epidural, birth, complications

“Visual field progression in patients with open-angle glaucoma”

Open-angle glaucoma is a lifelong, chronic eye disease causing deterioration of the field of vision. This thesis shows that in 15% of patients, this condition results in severe visual impairment by the end of the patient’s life. Specific patient characteristics can help determine which patients require ophthalmological treatment to reduce eye pressure. This thesis shows how these can be used to predict future deterioration of the field of vision. It has also been shown that many different methods with varying results exist to measure visual deterioration. A guideline is provided for deciding which method to use.

Key words:

eye disease, glaucoma, eye pressure, therapy

“Over gewichtige zaken”

“The danger of Innocence; common sense beliefs and misconceptions about false confessions”

In the last decade, overturned wrongful convictions have shown that false confessions are not a rare phenomenon.  Admitting to a crime one has not committed is seen as counter-intuitive by many people and studies have shown that the average person is not well informed about the possibility (and risk) of a false confession. The present dissertation demonstrates that misbeliefs and misconceptions about false confessions are a threat to innocent suspects and that there is a demand for changes in the process of police custody to make interrogations a safer place.

Key words:

false confessions, misbeliefs, misconceptions, wrongful convictions

“De stilte en de storm; 4 en 5 mei sinds 1945”

For almost 70 years, the Netherlands has remembered the end of the Second World and its victims War on 4 and 5 May. Despite the ideal of solidarity and unanimity that characterises these days, they often also include discussions and conflicts. What do we commemorate on 4 and 5 May and how do we do that? This historical study is about the ever-recurring discussions regarding the form content of these memorial days since 1945. It shows that 4 and 5 May have no intrinsic meaning. To this day, every generation has had to rediscover or reinterpret the significance of 4 and 5 May.

Key words:

Second World War, commemoration

“Deep Inferior Epigastric Artery Perforator Flap Breast Reconstruction: Optimization of Technique, Perioperative Measures, and Outcome”

“On Inner Warfare, the Host and the Adversary: Public Health Genomics of Chlamydia trachomatis and Human papillomavirus”

“Public Health genomics of infectious diseases – Insights gained from Chlamydia trachomatis infertility diagnostics”

“Molecular signatures and prognosis of HPV-positive head and neck lesions”

The increase in tonsil cancer in the US and Europe is attributed to infection with the human papilloma virus (HPV), especially HPV type 16. This thesis shows that roughly 35% to 40% of tonsil cancers are HPV positive, and that a specific protein, p16INK4A, is a good surrogate marker for the presence of HPV16. Previous research has revealed clinical differences between this and other tumour types; the present results show that at molecular level, too, these tumours should be considered a separate entity. HPV-positive tumours display fewer genetic abnormalities and a different expression of several key proteins involved in the regulation of cell division and cell death. Further, patients with HPV-positive tonsil cancer have better prognoses, with the exception of patients with HPV-positive tumours with genetic instability and over-expression of the protein EGFR. At present there is debate as to whether patients with HPV-positive tumours should be treated differently – in particular, less intensively – than patients with HPV-negative tumours. This thesis shows that caution is indeed advisable.

Key words:

tonsil cancer, human papilloma virus, prognosis

“SELF-MONITORING OF PHYSICAL FRAILTY: A proactive approach in community-dwelling elderly people”

Independent and healthy aging is important for many people. Preventing a decline in physical functioning can make a positive contribution to this. With this thesis, a monitoring and feedback system has been developed and evaluated, along with the elderly and care professionals, in which the elderly themselves can monitor changes in their physical functioning. The system consists of a scale that measures weight and balance, a grip ball that measures grip strength, and a mobile phone that can measure activity. Through a user-friendly application on the mobile phone, the system gives the elderly instant feedback when a decline is indicated. Steps can then be taken to prevent further deterioration or other negative health outcomes (such as falls, mobility problems or reduced autonomy).

Key words:

elderly; eHealth; self-management; physical vulnerability

“Towards a new, dynamic concept of health”

The WHO’s definition of health as a condition of ‘complete well-being’ is no longer sufficient for modern times. Therefore, Maggie Huber, together with ZonMw and the Dutch Health Council, developed a new definition of health as ‘the ability to adapt to and be able to independently manage the physical, emotional and social challenges of life’. Stakeholders such as patients, clinicians and policymakers provided feedback, and it seems that patients define health in very broad terms; social participation for them is just as important as physical symptoms. Based on this, Huber introduced the concept of ‘positive health’, charted along six key dimensions, including the spiritual/existential dimension and quality of life. The Dutch Community Health Services (GGD) is going to work with ‘positive health’, for instance, with measurement instruments and practical advice.

Key words:

WHO, health, new definition, nutrition research

“Collaboration in innovation: studies on the impact of collaborative innovation on firm performance”

“Islamic divorces in Europe; bridging the gap between European and Islamic legal orders”

This thesis addresses the issue of the recognition of Islamic divorces in European states.
Repudiation-based divorces are particularly notorious for their presumed violation of
fundamental rights of women and are consequently often not recognized. The resulting limping of legal relationships affects other fundamental rights of the persons involved, such as the right to marry and the right of free movement. For this reason, the author scrutinizes classical Islamic divorce law and the contemporary divorce laws and practices of Egypt, Iran, Morocco and Pakistan, as well as the Dutch, English and French recognition policies and relevant EU (case) law. By introducing various soft and hard law solutions, it provides legal practitioners with the information and tools to tackle major shortcomings in the recognition of Islamic divorces. This thesis is therefore a must-read for legal practitioners such as registrars, notaries and members of the judiciary, as well as academics.

Key words:

divorce, Islamic Law, (European) International Civil Law, European Law 

“The Impact of Brands on Innovation and Firm Performance - Empirical Evidence from Germany”

“Clinical and echocardiographic parameters to characterize atrial fibrillation”

Atrial fibrillation is the most common cardiac arrhythmia in the world. This type of arrhythmia can have serious consequences such as heart failure or cerebral infarction. This thesis describes new cardiac echo measurements which enable us to predict more accurately which patient will develop atrial fibrillation in the future, allowing early treatment to be started. If atrial fibrillation is already present, these measurements can indicate the stage of the arrhythmia and the chance of a certain treatment option being successful. Furthermore, an easy-to-use score has been developed which enables us to calculate the risk of worsening atrial fibrillation by using patients characteristics. 

Key words:

atrial fibrillation, echo measurements, predictions

“Electro-responsive hydrogels for vascular tissue engineering”

“Satellite cells in skeletal muscle atrophy and hypertrophy”

Ageing is accompanied by loss of muscle mass and muscle strength. This results in limitations in daily life, less independence and reduced quality of life. Muscle stem cells (also called satellite cells) are essential for muscle tissue growth and maintenance. This thesis shows that a reduction in the number of satellite cells and/or their function may play an important role in the loss of muscle mass associated with ageing. Long-term strength training helps increase muscle mass/muscle strength and is associated with an increase in the number of satellite cells. Strength training should be an important part of intervention programmes to prevent loss of muscle mass with ageing. 

Key words:

ageing, muscle mass, muscle strength, satellite cells

“Meat consumption and cancer risk; an epidemio-logical analysis from multiple perspectives”

Research shows that a high consumption of meat may increase the risk of certain types of cancer. To get as complete of a picture of this relationship as possible, this research looked at the effect of a vegetarian lifestyle on the development of cancer as well as at the mechanisms through which the consumption of meat possibly affects the risk of cancer. This dissertation shows that the complete exclusion of meat in our diet does not lower the risk of cancer. However, it also shows that it is important to make an informed choice regarding the type of meat consumed. For instance, heme iron, the substance that turns meat red, has been associated in our study with the development of colon cancer.

Key words:

meat consumption, cancer

“Cardiovascular drugs and the risk of systemic autoimmune diseases: Pharmacoepidemiological and experimental approaches”

“Managing anticoagulant therapies using innovative thrombin generation assays”

Thrombosis (undesired coagulation) can be treated with different types of anticoagulants. This thesis examines the effect anticoagulants have on the thrombin generation test, which registers the formation of thrombin. This enzyme is one of the key factors in the coagulation process. The more thrombin is formed, the higher risk of thrombosis; the less thrombin is formed, the higher risk of bleeding. One of the findings of this thesis shows that the whole-blood test has a predictive value for bleeding in patients taking oral anticoagulants. The results indicate that the thrombin generation test can be used to study anticoagulants and that more information is gained from this test compared to conventional tests.

Key words:

thrombosis, thrombin generation, anticoagulants 

“INNOVATIVE OPTICAL TECHNIQUES FOR INTRAOPERATIVE ANATOMICAL GUIDANCE; Surgical navigation beyond the limits of the human eye”

Innovative optical techniques can improve the intraoperative identification and characterisation of vital anatomical structures, such as nerves, ureters, arteries and bile ducts. This is crucial in all sorts of surgical procedures, as misidentification of these structures can lead to iatrogenic injury. This thesis focuses on two optical techniques: near-infrared fluorescence imaging using exogenic contrast for the identification of bile ducts, arteries and ureters; and diffuse reflection spectroscopy using endogenic contrast for the identification of new spectral contrasts of ureter, artery, parathyroid and nerve tissues that are invisible to the eye. While both techniques are subject to limitations, they have the potential to improve surgical care through better anatomical recognition. In addition, the newly discovered endogenic spectroscopic tissue contrasts provide insight into the development of a new generation of surgical cameras.

Key words:

surgery, optical techniques, navigation, anatomy, iatrogenic injury, safety

“Punitive Damages; The Civil Remedy in American Law, Lessons and Caveats for Continental Europe”

This thesis considers whether the civil law sanction of punitive damages has a future in continental Europe. To date, this form of civil damages has only been recognised in legal systems in the common law tradition, such as the USA, England, Wales, Australia and New Zealand. In these countries, the defendant in a civil procedure can face punitive damages in addition to compensatory damages. The functions of this private law penalty go beyond mere punishment and prevention; they also include protecting the public interest, facilitating private vindication and compensating costs borne by the plaintiff, such as legal fees. In recent years there seems to have been a change of direction in the European debate, with widespread reluctance increasingly giving way to new, less negative views on punitive damages. This thesis aims to contribute to this debate by enhancing insight into the operation, scope and significance of punitive damages.

Key words:

civil law, compensatory damages, punitive damages

“Sociale epidemiologie: schipperen tussen upstream en downstream”

“Pakistani Marriages and the Private International Laws of Germany and England”

The last decades, migrants entering Europe, brought their language, their culture and habits, but also their legal traditions with them. 
This thesis explores Pakistan, a country whose legal system raises many questions with respect to international family law matters, in particular in relation to marriages celebrated in Pakistan. 
The past and future migration of Pakistanis to Germany and England has inspired the interest in the topic of this thesis and the ambition to undertake an analysis of how the private international law of England and Germany deals with marriages celebrated in Pakistan. Next to its theoretical and scientific contribution, this thesis provides an essential resource of information for professionals that deal with Pakistani marriages, like barristers, civil servants and the judiciary. 

Key words:

Pakistan, marriage, international law

“The relationship between avoidable hospitalisation and primary care”

The aim of this study was to analyse the role of Primary Care (PC) in preventing hospital admissions for some types of conditions and the factors influencing the relationship between Avoidable Hospitalisation (AH) and Primary Care. The factors we found to play a role in the relationship between AH and PC were: the epidemiology of the conditions, the propensity to seek hospital care and the socioeconomic status of patients. Such factors were already known in the scientific literature, we also found that the organisational aspects of Primary Care have a crucial role. This study also permitted the estimation of the cost of avoidable admissions. When one considers the cost of these avoidable admissions, there is a clear need to better understand the factors that predict hospitalisation, especially in individuals with chronic disease. 

Key words:

Primary Care, hospital admissions

“Add-on ablation surgery in patients with atrial fibrillation; Drivers for Intervention”

Atrial fibrillation (AF) is the most commonly occurring cardiac arrhythmia in the Western world. Some patients who undergo open heart surgery have AF, and an additional procedure can be performed during surgery to relieve the AF. This thesis describes the effect of the additional surgical ‘microwave’ ablation technique on the various reasons or ‘drivers’ for treating AF. The study examined the influence of this additional surgical procedure on recovering normal cardiac rhythm following surgery, on the quality of life, cost-effectiveness, electrical cardioversions in cases of recurrent AF, and on the prescription of anticoagulant drugs. The treatment was shown to have no significant positive influence on any of these aspects. The new hybrid procedure, in which the electrophysiologist and the cardiac surgeon work in close collaboration, appears highly promising with regard to the future treatment of AF.

Key words:

atrial fibrillation, cardiac surgery

“Mechanisms and Imaging of myocardial injury and repair”