“Measuring personal autonomy and social participation in older adults with a chronic physical illness”​

“Samen sterk”

“Circulating Monocytes in Atherosclerosis: Local or Systemic Actors?”

“Exploring the nature of social preferences and their economic significance: four experimental studies”

“Health literacy: a neglected European public health disparity”

“Prenatal screening à la carte? Ethical reflection on the scope of testing for foetal anomalies”

New prenatal tests for discovering foetal abnormalities are being introduced more quickly in the screening process. This PhD dissertation examines the ethical implications of non-invasive, targeted and genome-wide prenatal tests. It appears that some tests are challenging the goal of prenatal screening, namely to enable pregnant women to make autonomous reproductive choices. Does the standard prenatal test offering therefore need to be reconsidered? This dissertation proposes an alternative: individualised choice. This means that pregnant women are offered a ‘menu of test options’ from which they can make choices that are best suited to their personal situations, standards and preferences. This does the most justice to their reproductive autonomy. The test offering will be limited by three factors: it must include severe disease-related abnormalities; the information should be adequate and not too complex so that an informed choice is actually possible; and the test may not generate findings that can harm the future child’s right not to know.

Key words:

prenatal screening, foetal abnormalities, ethics, reproductive autonomy

“Strategy-proofness and Single-dipped Preferences”

“Valorization in Public Health Genomics: A Conceptual Development from Technology Transfer to Healthcare Integration”

In the past decade we have seen an exponential growth of personalised medicine applications onto the market. However, it is noticed that their implementation into healthcare systems in the form of genome-based technologies has a huge backlog. By the time a technology reaches healthcare from the market, it can be considered irrelevant due to time lapse as a better technology emerges in the market. Consequently both industry and the citizens are at disadvantage. The thesis aimed to address this issue by developing a conceptual framework for covering the whole spectrum of translational research of (personalized) healthcare, with real examples. As a result, the model has been taken up in high level policy reports in the EU, best practice guidelines, grants, industry, publications and international conferences.

Key words:

Technology Transfer, Health Policy, Public Health Genomics, Personalised Medicine, Healthcare.

“Membership in International Organizations: Inequality among Equals”

“Long GnRH agonist protocol in IVF: approaches to optimizing treatment outcome”

“An analysis of health outcomes among sexual minorities with a focus on the HIV/AIDS epidemic among men who have sex with men in Belgium”

“Experimental Studies on New Therapeutic Approaches in Atrial Fibrillation”

Diabetes and obstructive sleep apnea are associated with increased recurrence of atrial fibrillation (AF). The present study was conducted to characterize the atrial substrate for AF in animal models for diabetes and obstructive sleep apnea and to identify new potential antiarrhythmic therapy strategies. Pharmacological inhibition of the enzyme CathepsinA attenuated structural alterations leading to increased atrial fibrillation-susceptibility in a rat model for diabetes. In obstructive sleep apnea, negative thoracic pressure during obstructive respiratory events is responsible for increased occurrence of atrial fibrillation, which was reduced by modulation of autonomic nervous system by renal sympathetic denervation but not by available antiarrhythmic drugs.

Key words:

Physiology, Atrial Fibrillation, Diabetes, Obstructive sleep apnea

“Energetics of the human mind; an effort to show the neural correlates of mental efforts”

“Fragmented Sleep – Fragmented Mind; The Role of Sleep in Dissociative Symptoms”

Title of the lecture of prof.dr. Ronald Knibbe:

“Roes en Ratio: sociaal epidemiologische aspecten van middelengebruik”

Title of the lecture of prof.dr. Dike van de Mheen:

“Zorgen voor morgen? The day after”

“Risk Stratification in Coronary Artery Disease; The Role of (bio)markers and Coronary CT-Angiography”

Cardiovascular diseases are the leading case of illness and death worldwide. Atherosclerosis (hardening of the arteries) leads to narrowing of the coronary arteries. With the aid of a CT scan of the heart, it is possible to gain more insight into the presence and severity of atherosclerosis. The CT scan can be used to make a diagnosis and also gives information about the prognosis. In this PhD dissertation, we have combined characteristics of atherosclerosis with certain substances (biomarkers) in the blood to better be able to estimate who is at higher risk of having a heart attack. 

Key words:

Cardiovascular diseases, hardening of the arteries, CT scan, biomarkers

“Clinical cardiac computed tomographic angiography implications for risk stratification”

In this dissertation the value of using CT coronary angiograms – a patient-friendly technique that produces images of the coronary arteries – on patients experiencing chest pain, has been researched. This technique appears to be more useful in predicting future myocardial infarctions and angioplasties than other techniques, such as stress tests. In addition to identifying arteriosclerosis, these scans also produce images of the artery walls. It is demonstrated how artery wall images provide us with important information that can be used to predict future infarctions. It is now possible to create detailed images of the coronary arteries and arteriosclerosis. This will help us identify high-risk patients that require more aggressive medical treatment.

Key words:

cardiac CT scan, diagnosis, prevention

“Ultrasound-guided foam sclerotherapy for treating varicose veins”

“The design of R&D alliance contracts” 

This dissertation contains four empirical studies in the field of research and development alliances (R&D alliances) and related contracts in the biotech and pharmaceutical industries. The basic research question was which factors or associated issues determine the manner in which R&D alliance contracts are formed between companies? More specifically, this dissertation examines factors that influence parties in an R&D alliance: (1) the allocation of control rights, (2) coordination between companies, (3) dispute resolution, if needed, and (4) recruitment. The results are especially important for companies that are interested in building alliances with other companies.

Key words:

R&D, contracts, strategic alliances

“Minimally Invasive Techniques in Foregut Surgery”

“Assessing Governance Assessments; The case of Mozambique governance assessments in the context of aid effectiveness discourse”

This case study builds on contemporary discourse on the relationship between governance, aid effectiveness and development. The findings suggest that the selected donor governance assessments portray a very similar image of the quality of governance in Mozambique despite their different conceptual and operational approaches. The assessments are seen as having contributed positively to governance in Mozambique by enhancing the voice of the non-state actors and by legitimizing their concerns. The impact of the governance assessments is, however, perceived to be undermined by the aid agencies’ restricted dissemination policies and top-down approaches. The way forward for assessing governance requires a shift from donor-led governance assessment towards country-led, joint assessments that build on country-specific analyses of what governance means, and towards a broad-based country ownership of the assessments processes and the results of the assessments.

Key words:

Governance, Aid Effectiveness

“Novel strategies for making myasthenia less gravis: targeting plasma cells and the neuromuscular junction”

“Hemispheric asymmetries in fronto-parietal networks underlying attentional control”

“Prostaglandins  and Phosphodiesterases in the Urinary Bladder Wall”

Overactive bladder syndrome occurs in about 1 of 6 people over the age of 40. Patients suffer from the sudden, irrepressible urge to urinate. They generally urinate often and usually have urinary incontinence. At present few effective medications are available. 
This PhD dissertation describes the search for new points of application for treatment through investigation in guinea pig bladders (which closely resemble human bladders). Maastricht’s research is the first in the world to demonstrate the use of the prostaglandin E2 receptors (EP1 and EP2) in the bladder wall. The prostaglandin system is best known as the active ingredient for medications such as ibuprofen and diclofenac. Secondly, this dissertation research studied and demonstrated the distribution of the phosphodiesterase enzyme in the bladder wall. This explains the effect of Viagra and Cialis on urinary symptoms, in addition to their known application for impotence. These results will hopefully lead to the development of new medications to treat overactive bladders. Thus Cialis was also recently registered as a treatment for overactive bladders in men.

Supervisor:

overactive bladder syndrome (OAB), prostaglandin, phosphodiesterase type 5 (PDE5), detrusor overactivity, incontinence, medications  

“Netwerken”

“Loco-regional control or breast cancer with an emphasis on the role of young age and lobular histology”

For a long time there has been doubt about the safety of breast conserving treatment for young women with breast cancer. Research over the past two decades, especially in recent years, has shown a strong improvement in local disease control with a recurrence rate of just 3.3% after five years. This improvement is mostly a result of the increase in both the use and effectiveness of adjuvant treatment such as chemotherapy and/or hormonal therapy. 
The current design of follow-up for young women after breast conserving treatment does not guarantee early detection of recurrence of the disease in the breast. This research shows that the recurring tumour is discovered in about 50% of the cases by the patients themselves. In a quarter of these cases, a local recurring tumour larger than 2 cm was discovered. This dissertation offers suggestions for improving diagnostics.

Key words:

breast cancer, breast conserving treatment, diagnostics, follow-up

“Working on activation; analyses of stories about vocational rehabilitation of people with disabilities in the Netherlands”

Key words:

Vocational rehabilitation; work disabilities; narrative research

“Peer Feedback to Enhance Learning in Problem-Based Tutorial Groups”

The success of the problem-based learning model, for which Maastricht University is known, depends amongst others, on the quality of the tutorial meetings. Unfortunately, this quality leaves something to be desired. This dissertation reveals that the quality of the discussions correlates with the student’s test scores. The dissertation researched whether students benefit from receiving peer feedback about their behaviour during tutorial meetings. One of the studies showed that the students who did not actively participate in discussions benefitted the most from peer feedback. A follow-up study revealed that male students in particular seem to benefit from this type of feedback.

Key words:

Problem-Based Learning, quality, peer feedback

“The Universal Periodic Review Mechanism of the United Nations Human Rights Council: Transforming the Human Rights Discourse”

The Universal Periodic Review (UPR) mechanism was created to monitor how well UN Member States comply with human rights obligations. Every four years, UN Member States report on the state of human rights within the country, hear ways to improve their human rights records and answers questions from fellow countries in a three-hour interactive dialogue. This dissertation concludes that the UPR process has the potential to transform the human rights discourse because states are, for the first time, answerable for all human rights obligations rather than just those rights covered under the conventions ratified by the country.

Trefwoorden:

mensenrechten, Verenigde Naties, universele periodieke doorlichting (UPR)

“The process of end-of-life decisions regarding people with intellectual disabilities”

Persons with an intellectual disability are often unable to take their own end of life decisions. Legal representatives, mostly family members, usually have a clear idea about the quality of life of the person with an intellectual disability and seem to feel very responsible themselves for taking these decisions. They find this difficult. Doctors find these people’s opinions extremely important but do not always make it clear that the doctor is ultimately responsible for these decisions. Doctors want to avoid conflicts with legal representatives and feel vulnerable themselves. A dialogue about this subject should begin far ahead of the expected end of life.

Key words:

intellectual disabilities, decision-making skills, end of life

“Studying biomarkers in populations at genetic and  clinical high risk for psychosis”

Very little is known about the biological process that leads to psychosis. What we do know is that the presence of dopamine in the brain is a likely contributor. One of the problems when researching this issue is that the disease process itself also triggers biological changes. This dissertation researched two patient groups not currently experiencing psychotic symptoms, but with an increased risk for developing them: (1) a group of clinically high-risk adolescents; (2) a group of genetically high-risk adults. The results show that severe pre-psychotic symptoms in individuals at increased clinical risk for developing psychosis are strongly correlated with high levels of dopamine in a specific area of the brain known as the striatum. Dopamine disruption therefore appears to predate the onset of initial psychotic symptoms.

Key words:

psychosis, risk, biological changes, dopamine

“Epigenetic regulation of BDNF-TrkB signaling in the pathophysiology and treatment of mood disorders”

“From Reaganomics to Eurocrisis: 30 jaren in Maastricht”

“Management of late preterm prelabour rupture of membranes”

When a pregnant woman’s membranes rupture between three and six weeks before her due date, it is preferable to take no action rather than to artificially induce. The risk of infection does not increase when no action is taken and a premature birth may result in additional complications. That is the main conclusion of this PhD dissertation, which followed more than 1000 women with broken membranes through a collaboration with 60 Dutch hospitals. However, for women who had Group B streptococcus (bacteria) in their vaginas, artificial induction seemed to make sense. Further research into this is needed.

Trefwoorden:

zwangerschap, voortijdig vliezen breken, kunstmatig inleiden

“Adiposity in COPD”

“Adding eyebrows to CSCL; understanding the combined use of synchronous and asynchronous communication and the role of motivation in computer-supported collaborative learning”

In addition to email and discussion forums, students can now also communicate and collaborate via videoconference environments. This PhD dissertation investigated how students use the possibilities of synchronous communication during weekly videoconferences and asynchronous communication with text messages outside the videoconferences, and how that relates to their satisfaction, motivation and learning outcomes. Despite the fact that synchronous communication is more ‘social’, students’ satisfaction did not increase and their performance was lower in the years when the videoconference system was used compared to the years when only asynchronous communication was used. However, indications were found that the use of the videoconference system decreased the differences between intrinsically and extrinsically motivated students with regard to the quantity and quality of asynchronous communication.

Key words:

online collaborative learning, videoconferencing, motivation

“Why Jamaica wants to protect Champagne: Intellectual Property protection in EU bilateral trade agreements”

“Stock Market Dynamics of Marketing Decision-Making”

Recent anecdotal evidence has stimulated much debate about whether the stock market enhances or impedes long-run firm investments in product innovation. Academic research, arguably, does not yet understand the stock market dynamics of public firm innovation behavior. This dissertation explores how firms manipulate their innovation and investments efforts in a response to stock market incentives. It is also investigated how public firms convey their innovation potential to the investor community, and how firms seek to improve communication channels with the investor community. Overall, the research outlines substantial and so far neglected costs of a stock market listing. These results offer implications for firms managing innovation activities and for economic institutions developing policies that guide firm behavior.

Key words:

firm investments, product innovation, stock market

“Voordat het wal het schip keert” 

“Is that your final answer ? How doctors should check decisions”

“Sexuality and Intellectual Disability; implications for sex education”

Despite the many problems that people with intellectual disabilities experience in the field of sexuality, such as difficulties forming relationships and experiences with sexual abuse, sexuality remains a neglected topic. This doctoral research shows that effective sex education programmes for people with intellectual disabilities are still not available in the Netherlands. Further, people with intellectual disabilities themselves can provide some new insights into what is important for sex education. Their carers also should be supportive in providing sex education. Finally, more research needs to be done into which methods are most effective for providing sex education to people with intellectual disabilities.

Key words:

intellectual disability, sex education, sexuality, Intervention Mapping

“Sexuality and Intellectual Disability; implications for sex education”

This dissertation investigates the link between the level and distribution of education and institutional change in societies where elites have a privileged access to political and economic organizations. Political elites should have sufficient skills to benefit from a modern economy and to respect property rights. However, more education of the general population might not necessarily contribute to stable property rights if income is not growing at the same time. Ethnocentric organizations are one of the reasons why a certain group of elites continues to dominate society in many developing countries. A case study on Kenya shows that the role of ethnicity in society depends on initial within-group inequality as well as the history of state formation.

Key words:

education, elite, ethnocentrism, Kenya

“Where borders and health care meet: Five studies in movements between health care systems”

National health systems have been conceived to fund, organise and deliver health care services within the borders of the domestic territory.  Why then do Dutch health insurers make contracts with Belgian hospitals?  Why do Californians go to Mexico for medical care, and Indian doctors migrate to the UK?  On our doorstep, more than 90% of German students at Maastricht University go back home when they need to see a doctor, while the Academisch Ziekenhuis Maastricht and Universitätsklinikum Aachen share surgeons, patients and equipment across the border. Whether globally or locally, these movements signal that health care is no longer a national affair. This thesis explores why and how health care actors make use of new options outside national health systems, and looks into the developments, such as increased mobility, European integration and the introduction of market mechanisms to health care, which are driving this change.

Trefwoorden:

health care, cross-border

“Combating the Dark Side: Managing Performance Reinvigoration of Long-Term Relationships”

“Complementarity in Innovation and Development; A Cross-country Comparison”

“Plantar pressures in diabetic polyneuropathy; the influence of gait pattern and exercise therapy”

“Moleculair spoorzoeken in ontspoorde cellen”

“Empirical Investigations of Costs and Benefits of Vocational Education and Training”

“Primary prevention of asthma among children”

An estimated 115,000 Dutch children suffer from asthma. There is no known cure but arresting the disease at the earliest stages is a goal.  It seems that prevention with several components (multifaceted) is more clinically effective than prevention with just one component (unifaceted); but it is not known if it is also cost-effective.  This dissertation looked at risk factors for asthma among six-year old children and examined the cost-effectiveness of various prevention programmes.  The conclusion is that asthma among first-degree family members significantly increases a child’s asthma risk, which is almost trebled when parents also smoke in the first post-natal year.  More importantly, multifaceted primary prevention can be cost-effective and preferred over usual care and unifaceted prevention.

Key words:

asthma, children, prevention, risk factors

“Social Threat Hurts! The influence of social threat on pain”

“Rescuing Modernity; global heritage Assemblages & Modern Architecture in Africa”

UNESCO aims to tackle Africa’s underrepresentation on its World Heritage List by inscribing instances of 19th and 20th century modern architecture and urban planning there. But, what is one to make of the utopias of progress and development for which these buildings and sites stand? After all, concern for ‘modern heritage’ invariably – and paradoxically it seems – has to reckon with those utopias as problematic futures of the past, a circumstance complicating intentions to preserve a recent ‘culture’ of modernization on the African continent. The present dissertation introduces the concept of global heritage assemblages to analyze this problem. Based on multi-sited anthropological fieldwork, it describes how various governmental, intergovernmental and non-governmental actors engage with colonial and post-colonial built heritage found in Eritrea, Tanzania, Niger and the Republic of the Congo.

Key words:

UNESCO World Heritage, Africa, global heritage assemblages

“Peri-operative Atrial Fibrillation in Cardiac Surgery; Impact on outcome”

“Effects of developmental fluoxetine exposure on neurobehavioral outcomes”

Depression during pregnancy and in the post-natal period occurs in 20% of women. A large number of women take antidepressants, mainly Prozac, during this period. The effect that the stress during pregnancy in combination with Prozac has on the offspring has hardly been investigated. In this study, pregnant rats were subjected to stress, after which they were administered Prozac with the active ingredient fluoxetine in the post-natal period. The effects on the offspring were examined with relation to depressed and anxious behaviour, the stress system, the hippocampus and sexual behaviour. Among other things, fluoxetine normalises the effects of prenatal stress on depressive behaviour. Without exposure to stress, fluoxetine inhibits sexual behaviour in male offspring and stimulates sexual behaviour in female offspring.

Key words:

post-natal depression, antidepressant

“Active Ownership”

This dissertation presents the latest empirical evidence on shareholder engagement strategies which can be used by shareholders to control managerial behaviour and to promote sustainable business practices. It postulates that the shareholders should become active owners and raise their voice if they are discontent with corporate performance or corporate environmental and social standards. Specifically, this dissertation discusses shareholder resolutions and direct private engagement tactics which shareholders can use to improve corporate governance, social and environmental behaviour. The main conclusion is that shareholders should realize that they can promote better environmental, social, and governance standards at corporations they invest in.

Key words:

shareholder engagement strategies, sustainability, managerial behaviour

“Assessment of clinical competence: Reliability, Validity, Feasibility and Educational Impact of the mini-CEX”

“Towards a learner-centred approach to postgraduate Communication skills teaching”

Teaching communication skills (CS) to junior doctors during postgraduate training remains problematic. Direct observation of junior doctors followed by feedback is a powerful way to teach CS in clinical practice. However, little is known about the effects of training supervisors on how to give feedback to junior doctors about their patient CS. In this study, a training program for supervisors on how to teach CS was designed and tested with clinical supervisors. It proves to be feasible, appreciated and effective in that it changes perceptions and behaviours and helps shift a paradigm change from a teacher centred to a more learner centred approach. To enhance transfer, training must be closely linked to formal and informal opportunities to practice teaching CS and supervisors should be able to join a community of teachers where exchanges of experiences can take place.

Key words:

teaching communication skills, doctors, postgraduate

“Learning to be the patient advocate. The development of a communication skills course to enhance nurses’ contribution to the informed consent process”

“Explaining Suicide in South African Adolescents: Psychosocial and environmental precursors” 

“Plus Ultra”

“Mechanisms of cardiovascular disease in the Metabolic syndrome and type 2 diabetes mellitus: Focus on adverse intermediate phenotypes”

“Perfect Equilibrium in Infinite Games”

“Optimizing Chlamydia trachomatis and Treponema pallidum diagnostics” 

The expression ‘assumptions are the mother of all mistakes’ certainly applies to sexually transmitted infections (STIs). Therefore this PhD dissertation examines a number of assumptions about the diagnostics of STIs. It was shown thatChlamydia trachomatis DNA is extremely stable in various preservation conditions; this knowledge is very important because, for example, a lot of research is being carried out with (old) frozen materials from patients. In addition, the quick tests for detecting Chlamydia trachomatis were evaluated. These proved to be very insensitive and thus unreliable, even while some of them were freely available on the internet! Optimising diagnostics can contribute to reversing the prevalence of STIs.

Trefwoorden:

SOA, Chlamydia trachomatis, diagnostiek

“Psychogenic non-epileptic seizures; a separate disorder or part of a continuum?”

“Antipsychotic-induced hyperprolactinemia in children and adolescents with mainly autism spectrum disorders. Prevalence, symptoms, clinical consequences and genetic risk factors”

“The World Starts With Me; promoting sexual and reproductive health and rights of adolescents in Uganda”​

“Partnering for mobility? Three-level games in EU external migration policy”

“Retinal detachment surgery: pre and postoperative prognostic factors”​

“Kidney donation after cardiac death - exploring Quantity and Quality”

“The effects of constituents and the food matrix of dairy products postprandial metabolism in overweight subjects”

“Preïmplantatie Genetische Diagnostiek: ongekende mogelijkheden”

“The Merits of Videolaryngoscopy during Glottic  Visualisation for Endotracheal Intubation”

“Dendritic cells in hyperlipidemia-associated atherosclerosis”

“Hypoxia-Induced Metastasis: The Role of the Unfolded Protein Response”

“Modulation of rental ADMA handling in hypertension”

“Energiebalans in beweging”

“Acknowledging Patient Heterogeneity In Health Technology Assessment”​

“The association between work stressors and cardiovascular disease, a methodological approach”​

“Stretch-mediated cardiac hypertrophy and extracellular matrix remodelling”

“Gezondheid”

“An economic perspective on school dropout prevention using microeconometric techniques”

“The role of sensory modality in age-related distraction”​

“Platelet-derived microparticles in vascular inflammation”

“On the molecular pharmacology of endothelinA Receptors or how EndothelinA agonists can make a difference”

“Patiëntpreferentieonderzoek in Health Technology Assessment en besluitvorming: van wikken, naar wegen”

“Power, control and coalition formation”

“Intention-based Decision Support; A new way of representing and implementing clinical guidelines in a Decision Support System”

“Parliamentary Immunity; A comprehensive study of the systems of parliamentary immunity of the United Kingdom, France, and the Netherlands in a European context” 

“Informal Patient Payments in Central and Eastern European Countries”​

“Endovascular repair of Acute and Paraanastomotic Abdominal Aneurysms”

“Van junglepraktijk naar oogtoren”

“Socializing Europe – Solidifying EU Citizenship”

“About goats, girls, boys and the bees”

Sexuality is a taboo subject in many countries in Africa and Asia. Not talking about it can lead to problems, among others for young people who become sexually active or unplanned pregnant. In her dissertation 'About goats, girls, boys and the bees' Joanne Leerlooijer shows that sexual education of school going youth in Thailand (The World Starts With Me) can contribute to breaking these taboos. She also shows that the Teen Mother project ‘Adopt a Goat’ in Uganda can break taboos about pregnancy of unmarried teenage girls so that they can continue their elementary or secondary education.  

Key words:

Human rights, sex education, Uganda, Thailand, teenage pregnancy

“The macroeconomic impact of a three-pillar pension system: the case of the Netherlands”

“The Pathogenesis of Panic Disorder”

“Mind the Gap; experimental studies on splanchnic hyperfusion and gastrointestinal integrity loss in man”

“IT Governance Transparency: an empirical assessment of information disclosures on IT governance”

Recognizing that firms are becoming increasingly dependent on Information Technology (IT) assets to achieve operational and strategic goals, it can also raise important issues, such as effective IT decision making and management control, IT investment priorities, and IT risk management. Information disclosure on the aforementioned activities can help the different stakeholders of a firm (for example, customers, investors, analysts) to assess the quality of IT governance activities. The dissertation contributes with a comprehensive IT governance disclosure framework to better understand how firms communicate their IT governance activities. 

Key words:

IT governance; Transparency; Corporate governance

“Explorations of Pelvic Floor Ultrasound”

“Cardiomyopathy and muscle insulin resistance in type 2 diabetes; Craving for sugars, or dying for fat?”

“Community Based Education and Professional Competencies: A study of institutional structures, perspectives and practices in Pakistan”

This thesis concerns Community Based Education (CBE) within the undergraduate medical and nursing programs. Presently, bulk of literature on CBE is devoted to describe what it is and its various models implemented world-wide.   However, there is little advice on how to effectively integrate CBE in Health Professions Education (HPE), therefore, in this context four research studies were carried out in various HPE institutes and health care settings of Pakistan.  The perspectives and practices of policy makers, academic leaders, faculty and graduates were explored to recommend evidence based revisions in curricula and instructional designs for effectively integrating CBE in undergraduate HPE programs.

Key words:

Community Based Education, Health Professions Education, Pakistan

“Clinical management of Rett syndrome”

Rett syndrome is serious development disorder caused by a genetic anomaly that only occurs in girls. In the Netherlands about 250-300 girls are known to have Rett syndrome. Besides serious mental disabilities, medical problems complicate this disorder, such as epilepsy, autonomous dysfunction and growth retardation. Since curing is not possible up to now, this dissertation focuses on clinical management. Specific attention is given to the role of genetic mutation, the role of metabolic problems as a cause for malnutrition and the ageing process with Rett syndrome. This research was conducted in the Gouverneur Kremers Centre of the MUMC+ in close collaboration with the Terre Foundation and the Dutch and Belgian Rett associations.   

Key words:

Rett syndrome, genetics, clinical management

“Prevalence and spread of antibiotic resistant micro-Organisms in a cross border region”

Trefwoorden:

antibiotic resistant bacteria, prevention, spread, Euregion Meuse-Rhine 

“Job security in the Netherlands”

“Essays on International Banking and (In)Stability in Financial Markets”

“Welke lijn trekt de cardioloog”

“Temporal patterns in the pathophysiology of Dialysis patients: an epidemiological approach”

Hemodialysis is the most commonly used treatment modality for patients suffering from end-stage renal disease (ESRD). This thesis primarily deals with longitudinal patterns in dialysis patients and their relationship to patient outcomes, such as survival and hospitalization. We address various oscillatory and non-oscillatory patterns in patients with ESRD. Oscillatory patterns are trends that repeat themselves over time such as circadian or seasonal patterns and they are covered in the first two chapters. Non-oscillatory patterns such as trends before or after certain events are covered in the remainder of the thesis. We also discuss new global database initiative, called MONDO, with aims of studying and improving outcomes of dialysis patients worldwide. The key conclusion of the thesis is to stress the importance of longitudinal trends in dialysis patients

Key words:

hemodialysis, renal disease, longitudinal patterns

“Physiology & pathophysiology of human brown adipose”

“Dietary manipulation of fat metabolism in relation to obesity and insulin resistance”

The epidemic of overweight and obesity is spreading fast over the whole world and involves an increased risk of diabetes. This dissertation studies how obesity and diabetes can be prevented by influencing the fat metabolism with the help of nutrition. Raised consumption of nutrition/food supplements such as resveratrol (polyphenol in red wine), unsaturated fatty acids (fish oil) and an increase in certain food fibres have positive effects on the fat metabolism and insulin sensitivity. These findings can contribute to a successful lifestyle intervention, favourable metabolic effects and the prevention of diabetes. 

Key words:

obesity, diabetes, fat metabolism, nutrition 

“It’s about time”

“Childhoods embargoed: constructing and reconstructing multidimensional child poverty in Iran, 1984-2009”​

“Expropriation and restoration of real property rights in the Federal Yugoslav Republic of Macedonia and in the Republic of Macedonia (FYROM): a legislative-historical study”

“Caregivers’ experiences with aggressive behavior of nursing home residents” 

The main goal of this dissertation was to explore caregivers’ experiences with resident aggression in nursing homes in Switzerland. Results demonstrate that the prevalence of experienced resident aggression is high for caregivers. Respondents perceive aggression as burdening and mentioned its adverse influence on the relationship between caregiver and resident. Furthermore, the findings reveal a need for action regarding the development of caregivers’ competencies in a comprehensible assessment of conditions and factors which can contribute to resident aggression. The management of nursing homes should also be required to give attention to this issue, as the results strongly suggest that support form superiors improve caregivers’ use of measures in managing resident aggression recommended by guidelines.

Key words:

nursing home, aggression, caregivers’ experiences

“The BRIC States and outward foreign direct investment in services”

This dissertation investigated the international laws that have supported the flow of foreign direct investment in services from the emerging markets of Brazil, Russia, India and China. These countries have engaged in an increasing amount of services oriented investment in industries like telecommunications, finance and transportation and have accordingly begun to conclude bilateral investment treaties to open new markets and to protect investors abroad. The dissertation proposes a global treaty drawing on observed legal trends in treaties concluded by developed and developing states and which balances investor protection with public interest matters such as environmental protection, human rights and culture.   

Key words:

international law, services, direct investment, global treaty

“Self-testing: To do or not to do? Development and evaluation of a decision aid on diagnostic selftesting for cholesterol and diabetes”

“Kiezen voor publiek-private samenwerking”

“Reproductive options for couples at risk of Huntington’s disease”

In dit proefschrift wordt  het gebruik van prenatale diagnostiek en preïmplantatie genetische diagnostiek door paren met een hoog risico de ziekte van Huntington onderzocht. Een selecte groep maakte gebruik van de zogenoemde exclusie-test omdat de risico ouder zelf niet geïnformeerd wil zijn over zijn/haar aanleg voor de ziekte, maar de ziekte wel wil voorkomen bij het nageslacht. Paren bleken zelf goed in staat zijn tot weloverwogen reproductieve keuzes, mits counseling door een klinisch geneticus en psychologische begeleiding gewaarborgd is. Kort na de voltooiing van het proefschrift werd het verbod op exclusie preïmplantatie genetische diagnostiek voor de ziekte van Huntington in Nederland opgeheven. 

Trefwoorden:

prenatale diagnostiek, preimplantatie genetische diagnostiek (PGD), ziekte van Huntington

“Imaging the brain; neuronal correlates of cognitive impairment in children with frontal lobe epilepsy”

Children that suffer from epileptic attacks originating in the frontal lobe often show learning disorders, among which arithmetic, memory and attention.  Consequently, these children often have problems keeping up in school. With the use of advanced MRi techniques, the research for this dissertation established a series of causes for these learning disorders. In children with this type of epilepsy the communication between various brain areas appears weak and the structure of the brain network not efficient. The weaker the communication between these areas and the less efficient the structure of the brain network, the more serious the learning disorders.  

Key words:

epilepsy, learning disorders, MRI, brain

“New frontiers in sacral neuromodulation for functional bowel disorders”

“De theorie van Darwin, de wet van Wolff, de hypothese van Sapir-Whorf en het opleiden van artsen”

“Signaling Games: Theory and Applications”

“Contributory Negligence; A historical and comparative study”

Our modern approach of the doctrine of ‘contributory negligence’ of the disadvantaged party in indemnity claims of liability outside contract has been formed by a long history. This research comprises a detailed study and description of the origin and the historic development of the doctrine of the ‘contributory negligence’ from the Ancient History until today.  It contains a study of primary sources from the various periods in the history of law. Moreover, the research comprises a (short) comparative legal study of the main current developments concerning the doctrine of ‘contributory negligence’ in France, Germany and the Netherlands. 
This dissertation was realized with financial support of the NWO. 

Key words:

contributory negligence, illegal act, history of law, comparative law

“An in-depth vision on perception: neural mechanisms of shading and motion object cue processing”

“No time to waste: a glycogen synthase kinas 3ß-glucocorticoid receptor signaling axis illuminated”

“Tinnitus: A CBT-based approach”

Approximately 60.000 people in the Netherlands suffer to such an extent from tinnitus (the continuous hearing of phantom sounds) that they can no longer well function. This dissertation studies the effects of a cognitive behaviour therapy that has been developed by the PhD candidates together with researchers from Maastricht University and colleagues from Adelante audiology & communication. This clinical study followed 492 persons with tinnitus during a year. Half of these received the new therapy, and the other half was treated conventionally with audiologic sound therapy. The conclusion is that the cognitive therapy led to a significant improvement of quality of life. For the majority of the patients, this improvement already occurred after twelve weeks. Cima published about his findings a year ago in the renowned medical journal The Lancet. Other studies also show that mainly fear of the tinnitus and catastrophizing thoughts about tinnitus have a negative influence on the patients. 

Key words:

tinnitus, treatment, cognitive behaviour therapy

“Getting a grip on myotonic dystrophy type 1”

This dissertation describes a series of studies about cardiac problems and clinical outcome measures with myotonic dystrophy type 1, a genetic muscle disease with multi-organ complications.  In spite of the frequent prevalence of cardiac disorders, there is no consensus on the diagnostic and therapeutic approach of cardiac involvement and the risk of sudden death is insufficiently recognized. Patients appear to have a complex cardiac phenotype with both involvement of the heart muscle tissue and the conduct system, which leads to a higher risk of rhythm disorders. Moreover, myotonic dystrophy type 1 leads to muscle weakness which causes considerable limitations in daily life. It is necessary that good outcome measures are available to enable evaluation of the effect of interventions on the functional situation of the patient in clinical trials. The importance of new clinimetric methods is illustrated and during this PhD research new clinical measuring methods were developed.

Key words:

myotonic dystrophy type 1, cardiac problems, clinical outcome measures 

“Toets alles en behoud het goede – voedingsepidemiologie en paradigma’s in de wetenschap”

“Ondanks een onlosmakelijke samenhang”

“Neural dynamics of food reward; the influence of body weight; cue exposures and attention”

“Plaque angiogenesis and lymphangiogenesis: can small vessels influence atherosclerosis?”

Atherosclerosis is a chronic inflammatory reaction of the arteries that in later stages of the disease can cause the development of a stroke or heart infarct. The local formation of new blood vessels and lymphatic vessels appear to play a role in the development of atherosclerotic lesions and the tearing of those, although the exact role is still unclear. This dissertation has shown that new blood vessels that are formed in the development of atherosclerosis are more unstable than normal blood vessels, and can contribute via several mechanisms to an increase of inflammatory cells in the atherosclerotic lesion.  Newly formed lymphatic vessels, however, seem to protect against further development of atherosclerosis because these vessels remove inflammatory cells. These findings can ultimately lead to new methods for early diagnosis of unstable plaque and newer treatments that inhibit or prevent plaque growth, for example by the stabilization of plaque blood vessels. 

Key words:

atherosclerosis, blood vessels, lymphatic vessel

“Second generation endometrial ablation”

Heavy menstrual bleeding (HMB) has a large impact on the physical and psychological wellbeing of women. One of the treatment options is an endometrial ablation: during one single operation via the vagina the endometrial lining of the uterus is removed or destroyed. This dissertation shows that the bipolar endometrial ablation technique is superior to the hot water or balloon ablation in the treatment of HMB. The research also shows that it is acceptable to perform endometrial ablation around the cervix on an out-patient under local anaesthesia, so that an epidural or narcosis is not per se necessary. 

Key words:

heavy menstrual bleeding, treatment

“Compensating Ecological Damage: Comparative and Economic observations”

Environmental pollution and devastation accompanying rapid economic development have created not only alarming losses to human beings and property but also astonishing damage to the environment itself. The difficulties in assessment and the special legal status of natural resources make traditional tort law an insufficient solution for the protection and compensation of this so called ecological damage. This thesis tries to design a compensation system, with the interaction between regulations, liability rules and compensation mechanisms (such as liability insurance, direct insurance, risk sharing agreement, environmental funds, other guarantees and capital market) to both prevent and compensate for ecological damage. Three new compensation models are proposed in this research, mainly based on the desirability and feasibility of mandatory financial security system. In addition to briefly exploring the existing experience in international regimes, the US and the EU, this thesis provides both theoretical and empirical research on the Chinese compensation system as well, which the existing literature has largely neglected.

Key words:

ecological damage, compensation mechanisms, regulations, liability rules

“Les Organes Restreints des Organisations Internationales”

“Towards succesful Web-based smoking relapse prevention; the efficacy of a computer tailored program, Incorporation post-motivational components & an attentional bias modification program”

“Echocardiographic predictors for recurrence of ischemic mitral regurgitation after restrictive annuloplasty”

In patients with chronic ischemic mitral valve insufficiency, the closure of the mitral valve is disturbed by traction on the valve blades as a result of a heart muscle disorder by oxygen deprivation (ischemic heart disease). The standard treatment for these patients concentrates on both the ischemic heart disease by means of coronary bypass surgery, and the mitral valve insufficiency (MR), by means of a constricting ring that is attached to the natural edge of the mitral valve. Recent studies have shown that 30% of these patients don’t benefit from this intervention (MR recurrence). This research defines preoperative parameters for the selection of patients who will benefit from this intervention. 

Key words:

mitral valve insufficiency, preoperative parameters, patient selection 

“Parlementair onderzoek; een studie van het onderzoeksrecht in Nederland, het Verenigd Koninkrijk en de Verenigde Staten”

Faced with growing concerns over executive dominance and awareness of the need for proper mechanisms to hold the government to account, the Dutch parliament has increasingly used parliamentary committees of investigation since the early 1980s. Three decades later, investigations have become an established form of parliamentary scrutiny, although investigative committees are still only established on a temporary basis. This Ph.D. dissertation consists of a comparative study of the procedures and practices of parliamentary investigations of three national parliaments: the Dutch Parliament, the UK Parliament, and the US Congress. Each parliament's investigative powers are studied and analyzed with regard to legal and procedural arrangements as well as the way in which these powers are applied in practice, taking into account their constitutional and political contexts. Based on these studies, the dissertation provides recommendations for further development of the Dutch parliament's investigative function.

“Aneurysmal subarachnoid hemorrhage: imaging strategies and cost-effectiveness aspects in diagnostic work-up and post-therapeutic follow-up”

“Epigenetic Dysregulation and the Pathophysiology of of Alzheimer’s Disease”

“Epigenetic Regulation in Aging and Alzheimer’s disease: A translational perspective”

“Perinatal events and altered pain sensitivity in later life”

“Organ saving treatment after chemoradiotherapy for rectal cancer – MRI as a selection tool -”

Patients with locally progressed rectal cancer receive standard treatment of long-term chemo and radiotherapy (‘chemoradiotherapy’), followed by surgical removal of the rectum. In response to the chemoradiotherapy the tumour can for the greater part or even entirely disappear. For these patients, follow-up surgery might not be necessary, but only if we can reliably assess the response to the chemoradiotherapy.  This dissertation has shown that with reference to current standard imaging techniques the response assessment after chemoradiotherapy by means of new MRI techniques – diffusion weighed MRI and MRI using a new contrast agent, gadofosveset-trisodium – can be considerably improved. 

Key words:

rectal cancer, chemoradiotherapy, MRI techniques, follow-up surgery

“Rectal cancer: are we ready for a paradigm shift?”

“The detention of asylum seekers in the European Union and Australia; a comparative analysis”

This dissertation compares the laws surrounding the detention of asylum seekers in the European Union and Australia. It explores the circumstances in which the detention of an asylum seeker may occur or be prolonged, the mechanisms for the review of detention decisions, the legal standards surrounding conditions of detention as well as the alternatives to detention and proportionality. The research finds that States should not presume that asylum seekers will be treated in accordance with international human rights standards merely because of a State’s subscription to those standards and suggests that any such presumption should be able to be tested.

Key words:

law, detention, asylum seekers, human rights

“The External Dimension of the EU’s Migration Policy; Different Legal Positions of Third-Country Nationals in the EU A Comparative Perspective”

The EU has set out the objective of creating a common European migration policy to address challenges relating to the demographic change, labour market needs and irregular migration. The dissertation argues that this objective is, however, difficult to achieve under the current highly fragmented EU framework for migration law and policy. The dissertation aims to understand why certain non-EU nationals, such as Swiss nationals and EEA nationals from Norway, Iceland and Liechtenstein, hold a privileged legal status which translates into favourable entry, employment and residence rights. For a European Union that is inclusive and treats non-EU nationals as an integral part of the EU population – especially in difficult economic times – national and European policy makers should strengthen the rights-based approach for migrants, consolidate existent rules and make such rules more coherent and transparent, for instance by introducing an EU immigration code.

Key words:

immigration, non-EUthird-country nationals, EU migration policy, mobility  

“Multiagent Learning; Dynamic Games & Applications”

“Hippocampal plasticity and corticosterone: From dendrites to behaviour”

The components involved in learning and memory are information storage, encoding and retrieval. These are modulated by experiences in the environment and intrinsic signals such as hormones and trophic factors. In turn learning and memory processes are dependent on changes in neurons (dendritic morphology, number, response) and their connectivity. Recent research has investigated neuroplasticity in the hippocampus in relation to learning and memory processes. However, within the literature we can find some paradoxical effects in hippocampal plasticity that appear to be dependent on the memory task used and the stress these tasks may elicit. The same holds true for studies on the effects of spatial learning on synaptogenesis. Therefore the aim of the present research was to determine how corticosterone affects spatial memory and hippocampal plasticity.

Key words:

hippocampal plasticity, corticosterone, learning

“Evolution of laparoscopic techniques in Bariatric surgery”

This thesis evaluates the evolution of laparoscopic techniques in bariatric surgery. Included are topics such as the technical aspects to perform laparoscopic sleeve gastrectomy, the various laparoscopic conversions in patients with already restrictive surgeries like laparoscopic adjustable gastric banding,  and the technical evolution from conventional multi-incision laparoscopy to single-incision laparoscopy (SIL) in bariatric surgery. Considering the high number of bariatric procedures performed annually, the request of revisional surgery is increasing as well and revisional procedures are feasible to be performed by laparoscopy, achieving the different advantages of minimally invasive surgery. For revisional bariatric surgery, the selection of the appropriate procedure for each patient is fundamental and comes from the multidisciplinary counseling between dietician, psychologist, internist and surgeon. 

Key words:

obese patients, obesity surgery, laparoscopy, technique

“Early metabolic risk in COPD”

COPD is a chronic disease of the lungs, but affects the entire body. This dissertation shows that COPD patients often have too much belly fat, too little muscular mass and tired muscles already at an early stage of the disease.  Moreover, it is shown that the unhealthy lifestyle of COPD patients is not limited to smoking cigarettes; they exercise too little and eat too many fats and too few fibres. The combination of COPD-specific factors and the unhealthy lifestyle thus strongly increase the risk of diabetes and cardiovascular diseases. Future research will show whether a focused training and nutrition programme can decrease these risks.  

Key words:

COPD, lifestyle, diabetes, cardiovascular diseases

“A circle of improvement in bleeding management: from laboratory to clinic and back”

“Impacts of Government Incentives to R&D, Innovation and Productivity: A Microeconometric Analysis of the Québec Case”

The dissertation empirically assesses the effectiveness of direct and indirect government support to the private R&D investment of firms in Québec on their economic performances. The main results are that the level-based tax credit is less effective than the incremental R&D tax credit since it contains a deadweight loss. Firms which use public grants for R&D in conjunction with R&D tax incentives perform better in terms of R&D input additionally and productivity growth than firms that use only R&D tax incentives. Manufacturing firms in Québec that invest in innovation have a productivity that is comparable to that of OECD countries. Subsidized firms closer to the technology frontier spend more on innovation and earn more sales from product innovation than those further away.

Key words:

R&D, government incentives, public subsidies, innovation, productivity

”Investing in Early Childhood Care and Education: The Impact of Quality on Inequality”

This dissertation aims at informing policymakers about ways to invest in early childhood care and education. It adds important evidence on a number of quality characteristics (e.g. staff-per-child, share of trained / male / ethnic minority staff, and staff turnover) they may directly influence to stimulate child development. Policymakers have increasingly acknowledged early childhood investments as instruments to stimulate social mobility of children who are at risk of falling behind at school. Results of three studies on unique Dutch and Danish datasets indicate that better quality may well lead to positive outcomes. However, the new evidence is not sufficient to empirically justify the high hopes put in childcare investments and their social mobilization potential. So we cannot yet be certain that public resources are being effectively spent.

Key words:

childhood care, child development, social mobility

“The protection of non-economic interests in European competition law”

“The Relevance, Variability, and Malleability of Personality Traits”

“Radiologie in medisch onderwijs”

“Value-Based Decisions: Situational Influences and Neural Mechanisms”

In order to make complicated decisions, such as choosing between a holiday and a new car, it is necessary to find a way to compare these. This research shows that the brain computes an abstract value for each option, which allows comparison with any other option. At the same time, we observe that decisions across a wide range of situations are influenced by irrelevant context. For example, participants frequently change the amount of money they want to pay for an object. Understanding why people do this can uncover the mechanisms underlying decision making, and eventually help people make better decisions. 

Key words:

brain, neural mechanisms, decision making 

“Ambulatory Gait Analysis: Clinical application and fall risk detection”

This dissertation investigates if ‘Acceleration-based Gait Analysis’ (AGA) is suitable to describe the walking pattern of various populations. Also, the response after a perturbation during walking is closely studied. The conclusion is that AGA is reliable and sensitive to personal characteristics and health aspects. This, together with the practical advantages (ambulant, simple, fast), the objectivity and the detailed output show the added value of AGA for the clinical practice. The developed and validated trip set-up (Timed Rapid Impact Perturbation, TRIP set-up) can be used to study stability during walking and has shown that muscular power, cognition and walking speed alone have little influence on the response after a perturbation in the walking pattern.

Key words:

gait analysis, accelerometer, perturbation in walking pattern

“Body weight loss and maintenance as affected by environment and genetic predisposition”

“De kapitaalverschaffer zonder stemrecht in de BV”

On the implementation of the Act on simplification and greater flexibility of private (BV) limited companies (Wet vereenvoudiging en flexibilisering BV-recht) on 1 October 2012, Dutch law was introduced to shares without voting rights and to depositary receipts with or without the right to attend general meetings. This research is focused on the provider of capital without the right to vote. The legal position of the holder of shares without voting rights, the holder of depositary receipts with or without the right to attend general meetings, the holder of a participation certificate and the holder of shares whereby the right to vote has been transferred to the usufructuary or to the pledgee were analysed. Not only the rights of the provider of capital without voting rights were discussed, also the open standard of the corporate reasonableness and fairness regarding the provider of capital without the right to vote and his legal remedies were analysed. In this thesis recommendations for amendment or interpretation of the law were made. The pros and cons of the different legal concept without voting rights and point of interest for the use of these legal concepts in practice were put forward.

Key words:

private company law, shares without voting rights, depositary receipts with or without the right to attend general meetings

“Out of the Black Box”

“Postprandial  muscle protein synthesis in the elderly”

Old age involves loss of muscle mass. This dissertation describes a series of nutritional interventions that will be used to effectively raise the muscle structure in the elderly.   Physical exercise before meals is an effective way to achieve this. Also, the quality of the protein in the meals and the quantity play an important role. Quickly digestible proteins are more effective than slowly digestible proteins; particularly the consumption of whey protein (from milk) turned out to be very effective. The quantity of whey protein that has to be consumed in a single meal to raise the maximally raise the muscle structure amounts to 35 grams or more.

Key words:

muscles, old age, proteins, nutrition, milk, meat

“European Union Property Law; From fragments to a system”

The European Union’s internal market has enabled ever more people and companies to buy and sell property across borders. However, Member States’ laws governing property transactions vary, and do not allow parties to choose one country’s property law for their transaction. Adapting to different laws raises transaction costs, and differences between the countries’ property laws may result in a party losing their property rights. European property laws which can be used throughout the Union would therefore be helpful. The central aim of this dissertation has been to propose such European rules of property law.

Key words:

European law, property transactions

“The Ubiquitin Proteolytic System: From the Backyard to the Forefront of Biological Research and Clinical Applications”

“Childhood overweight: The influence of parenting on children’s energy balance-related behavior”

This dissertation studies the influence of education styles and specific parenting practices on the eating and exercise behaviour of children, because this influence appears to be considerable.  Due to a lack of reliable Dutch surveys for parents these were first developed and validated. Subsequently, parents from the KOALA birth study filled out these surveys for their children. Results show that food practices within a family have great influence on the eating behaviour of children.  Children eat healthier when parents are in control of what their child eats. Exercising pressure to eat more and giving food as a reward has a reverse effect. The effect of food rules on the eating behaviour of children further depends on the parenting climate at home and the child’s character (temperament and eating style). In a positive parenting context (characterized by care, structure and behaviour control), food rules have more effect than in a compulsory and overprotective home environment. The findings are important for the improvement of intervention programmes for parents with overweight children.  

Key words:

parenting, eating behaviour, children, overweight

“Ambulatory Rehabilitation in Patients with Spinal Cord Injury: a clinical perspective”

About 45% of patients with a spinal cord injury (SCI) recover ambulatory function within one year after the event. The thesis concentrates on recovery profiles of certain lesion types, the assessment of walking capacity and on robotic training of walking for severely affected patients. The included studies showed that patients with an incomplete SCI show marked recovery. Neural centers below the level of the lesion respond to targeted training which is of importance for the early phase when the symptoms of the SCI are most prominent. The progresses of walking function throughout the rehabilitation can be reliably and validly be assessed using clinical tests. Ambulatory training with robotic devices improves walking speed and endurance. Further studies are required to investigate the importance and feasibility of the training-intensity.

Key words:

spinal cord injury, recovery, walking capacity, robotic training

“Dynamic Cerebral Autoregulation: from methodology towards clinical application”

This dissertation studies the regulation of the blood flow of the brains. In various syndromes, such as after a brain infarct or with a head trauma, locally this regulation does not function sufficiently anymore. The aim of the research was to develop a simple measuring method to quantify the function of this regulation. In this method the blood pressure and the blood flow in the brains is measured non-invasively.  With the use of techniques from the signal analysis, the function of the regulation can be rendered with a few simple parameters. However, the reproducibility of these measurements is still not sufficient for a diagnostic test in the individual patient. The method can, however, be used to compare groups of patients.

Key words:

blood flow, brains, trauma, measurement

“The investigative function of the European Parliament; holding the EU executive to account by conducting investigations”

This dissertation studies the regulation of the blood flow of the brains. In various syndromes, such as after a brain infarct or with a head trauma, locally this regulation does not function sufficiently anymore. The aim of the research was to develop a simple measuring method to quantify the function of this regulation. In this method the blood pressure and the blood flow in the brains is measured non-invasively.  With the use of techniques from the signal analysis, the function of the regulation can be rendered with a few simple parameters. However, the reproducibility of these measurements is still not sufficient for a diagnostic test in the individual patient. The method can, however, be used to compare groups of patients. 

Key words:

European Union, control, parliamentary investigation

“Terug naar af met de GGZ? Pleidooi voor een innovatieve en duurzame psychische hulpverlening”

“Axillary treatment and risk of regional recurrence in breast cancer patients”

The sentinel lymph node procedure was introduced to breast cancer patients with the purpose of less often performing axillary lymph node dissections. In this procedure, the firs lymph nodes that receive lymph from the breast tumour are identified, removed and examined for metastases. Through intensive processing of the sentinel lymph nodes, smaller metastases (micrometastases) are more often identified.  If the sentinel lymph node does not contain metastases, no axillary lymph node surgery is performed. The question is if this is also safe with micrometastases in the sentinel lymph node. Not performing axillary lymph node surgery in this group is being related to an increased risk of metastases within 5 years. Axillary treatment is recommended for patients with sentinel lymph node micrometastases and unfavourable characteristics of the tumour, who don’t receive supportive systemic therapy. 

Key words:

breast cancer, metastases axillary lymph node, sentinel lymph node procedure

“Actus reus and participation in European criminal law”

“Same but different: Functional correlates of different psychopathy dimensions in (antisocial) youth”

“REIT Investment Decisions: Governance, Behavior, and Sustainability”

“Finding ways to promote STI testing among the Afro-Carribean community in the Netherlands”

Research has shown that each year more STI’s are found among the Afro-Caribbean community than among the other ethnic communities in the Netherlands. This may be caused by the travelling behaviour of this community to their country of origin, where they have unprotected sexual contact, and the by the fact that people in this community often have several partners. To prevent spreading early testing is important. Existing interventions to influence sexual behaviour appear not effective for the Afro-Caribbean community in the Netherlands. This study has shown that the social environment (parents, relatives, friends) have a great influence on the personal motivation to be tested for STI.  Interventions should therefore not so much focus on individual factors, but mostly on the influence of the social community. When people speak more openly about sexuality and encourage frequent testing, the negativity about testing would diminish.  

Key words:

STI, Afro-Caribbean community, prevention, intervention

“Can PDE inhibition improve cognition? Translational insights”

Cognitive restrictions belong to the most important symptoms of patients that suffer from neurodegenerative and psychiatric disorders, such as Alzheimer’s disease and schizophrenia. Despite the wide range of possible pharmacological targets the clinical effectiveness of these is generally low. Recently, there has been more and more attention for phosphodiesterases (PDEs) as a target for cognition improvement. This dissertation studies the effects of PDE inhibitors on cognition. The conclusion is that specific PDE inhibitors can indeed improve cognition, but that further translational research is needed to make an in-depth assessment of the full potential of these substances. In this further research extra attention should be given to differences between various kinds of treatment (for example acute versus chronic), the reversing of restrictions versus the improvement of healthy cognition and the behaviour tasks that are used. 

Key words:

cognitive restriction, pharmacological treatment, PDE inhibitors

“On neural integration of faces and sematics”

“Mapping the primate brain with network analysis”

“Sound Science; Recording and Listening in the Biology of Bird Song 1880 – 1980”

Science is generally regarded as a mostly visual practice in which the role of other senses is systematically minimized. Yet, certain scientific problems require specific sensory skills. This dissertation investigated in which way scientists use hearing techniques for their research. This was done on the basis of historical research into field recording practices of ornithologists and behavioural biologists in bio-acoustics, the study of animal sounds. One of the conclusions is that admittedly sound recordings increasingly disqualified human hearing as a faulty and selective instrument, but that a vigilant and experienced ear remained indispensable; for example to identify behaviour in the field or to interpret patterns in the lab. This study is part of a larger research into the meaning of the auditory element (listening) in science, which is historically considered less objective than the visual element (watching).    

Key words:

animal sound, cultural history, biology, listening, senses 

“Exbelt: expelling belt restraints from psychogeriatric nursing homes”

Earlier research at Maastricht University already showed that belt restraining residents of nursing homes is unnecessary and can even be harmful.  And yet, belt restraints are still common practice in many Dutch nursing homes. Therefore, the Maastricht research group developed the ‘EXBELT’ method to reduce and prevent belt restraints. This dissertation studied the effects of the method. The result is a considerable reduction of belt restraints and no new cases in nursing homes where EXBELT was applied. Two years after the introduction the use of belt restraints had even further decreased.  This was not the case in nursing homes where EXBELT was not introduced; there still 14% of the residents are belt restrained. This kind of long-term evaluation is unique worldwide and was never conducted before.   

Key words:

EXBELT, nursing homes, belt restraining

“Prevalence and resistance of the commensal flora in non-hospitalized patients”

Antibiotics resistance (insensitivity of bacteria to antibiotics) is an increasing problem, as is shown in many recent publications. Most studies on this issue are conducted in the hospital, whereas 80% of the antibiotics use takes place outside the hospital. This dissertation investigates the antibiotics resistance of two clinically relevant bacteria, namely Staphylococcus aureus (in nine European countries) and Escherichia coli (in the Netherlands), obtained via non-hospitalized patients. The conclusion is that the antibiotics resistance to these bacteria is currently limited in the extramural setting. The results of this dissertation can be used to optimize antibiotic therapy of non-hospitalized patients to keep antibiotics effective in the future.

Key words:

antibiotics resistance, extramural.

“Clinical and biomarker correlates of genetic risk factors for Alzheimer’s disease”

“Emotional states, crime, and violence; A Schema Therapy approach to the understanding and treatment of forensic patients with personality disorders”

There is little scientific evidence for the effectiveness of the treatment of patients in the forensic psychiatric system (TBS) with dramatic personality disorders.  This dissertation describes the extent to which Scheme Therapy elements and techniques can make a useful contribution to understanding these patients. A second focus of this dissertation was drama therapy, in which showing emotions is the main priority. Central element within the Scheme Therapy are the ‘scheme modi’, i.e. fluctuating emotional situations. The results show that criminal behaviour and its origin can be understood by defining this behaviour as consecutive scheme modi. Moreover, it turns out that Scheme Therapy and drama therapy are effective in consciously provoking scheme modi. If forensic psychiatric patients (TBS patients) and their delinquent behaviour are better understood, risk factors can be better treated. 

Key words:

Forensic psychiatric system (TBS), scheme therapy, emotions, personality disorders, violence

“Going beyond the ‘Grand Mean’; advancing disease management science and evidence”

The research shows that the treatment of diabetes patients in the Netherlands and many other European countries does not sufficiently focus on the patient.  Standardized guidelines, protocols and performance indicators weigh more heavily in the determination of treatment plans than the personal needs, wishes and possibilities of patients.  The research also shows that only a small group of patients, namely the ones with insufficient glycemic control, benefit from the care that is currently offered in family doctor practices. For the control of their diabetes, healthier patients benefit more from self-management than help from a family doctor. Recommendations for a more ‘integrated made to measure care’ are among others better support with self-management and adequate information technology.   
This research was for the greater part financed by the European Commission (DISMEVAL-project).

Key words:

diabetes patients, treatment by family doctor, self-management

“Vasculogenic mimicry in malignant tumors; tumor cells in disguise”

Aggressive tumor cells can obtain the ability to form vascular-like structures that may contribute to blood circulation and/or tumor cell metastasis. This process is referred to as vasculogenic mimicry. Our research was aimed at identifying novel key molecules implicated in this process. By these means, expression of CD44 –an important marker of cancer stem cells – was identified in vasculogenic tumor cells. Also, the importance of perivascular cells in vasculogenic mimicry is described. Although currently applied angiogenesis inhibitors have not proven to be effective against this malignant process, treatment of vasculogenic tumor cells with imatinib (Gleevec®) did hamper their ability to form vascular-like structures. This research increases our knowledge of vasculogenic mimicry and may contribute to the development of clinically more effective treatment strategies against cancer. 

Key words:

angiogenesis, cancer, tumor cell plasticity, vasculogenic mimicry, vasculogenesis

“Recovering memories of childhood sexual abuse; from cognitive mechanisms to classification”

“Afscheid van dezen en genen?”

“Unified yet separated; Empirical Study on the Impact of Hierarchical Positions within Communities of Learning”

Communities of Learning (CoL) are promoted to foster interpersonal knowledge transfer among participants of organizational training initiatives. However, past research has largely neglected hierarchical positions as a major obstacle to collaborative learning processes. Yet, in practice, evidence has shown that top management will exhibit a drive to dominate discussions and reinforce the prevailing status quo, while lower level management often has been found to face a certain fear of speaking up in front of their supervisors. This dissertation addresses this shortcoming by providing empirical evidence from 25 CoL of a global organization. The results clearly indicate that the higher participants’ hierarchical position, the higher their level of activity and the higher their performance. By incorporating these insights into future CoL, HRD managers can better design and facilitate collaborative learning activities that contribute to the learning experience of all participants, e.g. implement a mentoring system or instruct facilitators to pro-actively connect participants.

Key words:

communities of learning, learning process, hierarchical position

“Neurodevelopmental toxicity detection by transcriptomics in an embryonic stem cell differentiation assay”

For research into the possible harmfulness of chemical substances and medicines for fertility and the unborn child many laboratory animals are used. This dissertation describes the use of embryonic stem cells in a new test without laboratory animals, in which the effects of substances on the formation of nerve cells can be determined. The research focuses on the use of changes in gene expression as a measure for the effects of substances, and determines at the same time with the help of the ‘transcriptomics’ technique the gene expression of all genes. Substance-specific changes in gene expression appear to have predictive value for the harmfulness of the substances for the unborn child. This research makes an important contribution to both knowledge about mechanisms of harmfulness of substances and to the reduction of laboratory animal use in developmental toxicology.

Key words:

toxicity, embryo, stem cell test, ‘transcriptomics’

“Deep brain stimulation and the cerebellum”

“Lipid droplet coat proteins, skeletal muscle lipid metabolism & insulin sensitivity”

Steatosis in muscles plays an important role in the development of insulin resistance, an obesity-associated early stage of type 2 diabetes.  However, also endurance trained athletes show a high degree of fat storage in the muscles, even though athletes are in fact highly insulin sensitive. This suggests that not the extent of fat storage but the characteristics and localisation of this muscle fat determine whether it disturbs the insulin signal cascade.   
This dissertation shows that the muscle cells of type 2 diabetes patients have an intrinsically reduced capacity for the neutral storage of fats in lipid droplets. Moreover, it was shown that the creation of storage capacity for neutral lipids protects against obesity-associated insulin resistance in the muscle.  In rats, increasing the presence of the lipid droplet proteins perilipin 2 (PLIN2) or PLIN5 in the muscle led to an increased fat storage in lipid droplets without negatively influencing the insulin sensitivity of the muscle. Further research into interventions that positively influence the PLIN function and consequently the fat storage capacity – such as pharmacological, nutritional and exercise strategies – are therefore promising in the framework of prevention and treatment of type 2 diabetes. 

Key words:

type 2 diabetes, muscle, lipid metabolism, fat, obesity.

“Lifestyle and arterial stiffness in young adults: A life-course approach”

“Electronic mobility aids for persons who are visually impaired”

Persons who are severely visually impaired or blind can use, besides the well-known ‘white cane’ or a guide dog, Electronic Mobility Aids (EMA) to move independently outdoors. These aids offer support with obstacle detection, orientation and navigation. This dissertation gives an overview of available EMA and provides insight in their usability, functionality and effects on the mobility of the user. For measuring the usability and functionality, and for measuring the effects new methods were developed. Based on the results of the research an advisory protocol has been developed for the supply of EMA in practice. This has been implemented in organisations that provide care for the blind and the visually impaired. 

Key words:

visual impairment, blindness, Electronic Mobility Aids (EMA)

“Enhanced Prediction and Prevention of Drug-Induced Torsades de Pointes”

Over the last decades, drug induced cardiac arrhythmias, including Torsades de Pointes (TdP) have become a major issue in drug development. There is a pressing need for better understanding of the mechanisms involved in TdP manifestation to allow for enhanced prediction (via more predictive surrogate markers) and prevention of this arrhythmia (via novel targets). This thesis elucidates a number of cellular mechanisms involved in beat-to-beat variability of repolarization, which is one of the newer surrogate markers thought to have utility in predicting this arrhythmia. The thesis highlights the role of calcium release from the calcium store within the single myocyte in altering this parameter. Additionally the dissertation illustrates the link between mechanical and electrical activity under specific conditions and provides further validation of an additional novel marker for proarrhythmia (the electro-mechanical window). Finally, research contained within this thesis suggests antiarrhythmic strategies for the development of novel therapeutic agents.

Key words:

cardiac arrhythmias, drug development, cellular mechanisms, markers

“Novel Perspectives in Regulation of Chondrogenic Differentiation”

The joints contain cartilage that allows them to move swiftly. When cartilage is damaged by a trauma or osteoarthrosis, this often difficultly recovers. This research wants to find new ways to stimulate cartilage formation from stem cells and to prevent undesired ossification. It is shown that a short and very mild inflammatory reaction (as in a wound healing process) is capable of stimulating cartilage formation, that physiological environmental factors of cartilage play a regulatory role in the cartilage formation process, and that the medicine celecoxib can prevent ossification. These results contribute to the optimization of cartilage regeneration techniques.  
This research was co-financed by the Reumafonds and the Annafonds.

Key words:

cartilage, regenerative medicine, stem cells, osteoarthrosis and orthopaedics

“OLD TIMES AHEAD; The Dawn of the Ageing Consumer”

In ageing Western societies older people become increasingly important for companies’ sustained success, because older people form a big and attractive market segment. This PhD research shows that the prevailing stigma of older people being poor, frail and old-fashioned, is often incorrect – many 50plus consumers are healthy, wealthy, active and curious.  In order to serve the older consumer appropriately, companies and researchers need to understand what characterizes the older consumer. For example, older people base their decisions on their experiences and they consider fewer alternatives than younger people. Older consumers are also more reluctant to believe ad claims than younger consumers. This information helps marketers in their communication strategies.

Key words:

50plus consumers, characteristics, marketing strategy

“The Triple Burden of War; an assessment of the mental health status and coping strategies of Sudanese female undergraduates for developing a psycholsocial counselor training program”

The current Darfuri crisis and the associated mental health burden have warranted the investigation into the mental health status of two groups of Sudanese female undergraduates: War-affected Darfuri and non-war-affected Omdurmani.
Darfuri female undergraduates had high levels of emotional distress that were strongly associated with the prevalence and severity of post-traumatic stress disorder, whereas Omdurmani students faced the ‘normal’ tertiary challenges of undergraduate life. However, both student groups showed similar levels of major depression disorder and generalized anxiety disorder.
Resilience levels and coping strategies differed; Strong religious practices, the ability to form interpersonal relationships and a positive future outlook seemed to lend to Darfuris the ability to cope. Omdurmanis however were more likely to use leisure activities, were more self-reliant and preferred being alone. This research will be used to design a culturally relevant war-trauma counsellor training program that can be used by educational institutions throughout Sudan.

Key words:

vrouwen, copingstrategieën, oorlogstrauma, opleiding voor adviseur

“Institution and Corporate Governance”

“Integrated Chronic Care for Patients with Atrial Fibrillation”

“Brain in Sight: probing the neural dynamics Underlying conscious vision”

Which processes in the human brain are responsible for conscious vision? The visual system consists of several areas that each play a certain role in the representation of our perception. This research used several methods to study this large network at various levels. Magnetic stimulation of visual brain areas, for example, was used to disturb perception, brain scans were used to examine the communication in the brain during visual tasks, and new experimental manipulations offered insight in fundamental interactions between information streams of our two eyes. Integration of these different perspectives is necessary to realize a complete picture.

Key words:

vision, brain

“Doorbreking van de natrekking: in rechtsvergelijkend perspectief”

“Van paradox naar behandeling: het oude renine-angiotensine systeem in een nieuw licht”

“Screening for hepatitis C virus infection of individuals at risk hidden among the general population”

“The glutaredoxin 1/protein S-glutathionylation axis in inflammatory lung disease; in vitro to clinical characterization”

“Intranasal delivery of rapid acting drugs”

“Pien, douleur of schmerz?”

“Bot en afweer: partners of rivalen?”

“Encoding of natural sounds in the human brain”

In everyday life, we are surrounded by sounds that convey language, emotion, and other vital information regarding our environment. This thesis describes studies that use functional magnetic resonance imaging (fMRI) to investigate how incoming sound waves are processed in the human brain. The results show that throughout the human brain multiple orderly representations of sound frequency (tonotopic maps) exist. Furthermore, neuronal populations are finely tuned to combinations of behaviourally relevant frequency bands. This selective tuning may reflect neuronal filtering mechanisms operating to transform tonotopic sound images into higher-level, behaviourally relevant representations.

Key words:

natural sounds, fMRI, human audition, tonotopic maps 

“Assessing outcomes of liver surgery: current status and future prospects”

Atrial fibrillation (AF), a common cardiac arrhythmia, is a chronic disorder. This research studied the effectiveness of an integrated approach of this patient group:  an outpatient clinic for patients with AF (AF outpatient clinic), under the direction of nurses, based on guidelines and supported by software.  
A randomized scientific study among 712 AF patients (comparison of AF outpatient clinic and regular care) showed a significant improvement of compliance with evidence-based guidelines, which resulted in a significant reduction of cardiovascular hospitalizations and mortality in the AF outpatient clinic in comparison to regular care. Moreover, this approach is cost-saving.  Practically speaking, this extensive intervention, aimed at patient information, guidelines and teamwork is the key to success. The results confirm the statement that an integrated approach of chronic care can prevent future capacity problems and extremely high costs.

Key words:

chronic care, integrated approach, atrial fibrillation

“Vitamin D and Multiple Sclerosis: immunological and clinical outcome”

“The power of simple scheduling policies”

“Culture matters in medical schools: How values shape a successful change”

“Public Health Technology Assessment: niet horen, niet zien en zwijgen!”

“The role of primary and secondary care in the management of pulmonary embolism: a shifting paradigm?”

“Measurement and Determinants of Adherence to Antiretroviral Therapy in Northern Tanzania: Opportunities for Improving Treatment Outcomes”

“Adjustable gastric banding, sleeve gastrectomy and Roux-en-Y gastric bypass by laparoscopy: long term outcomes and laparoscopic solutions in case of failure”

“Out-of-pocket patient payments for health care services in Hungary: Past experience and future perspectives”

“Samen zorg dragen”

“The assessment of cardiovascular risk for primary prevention in the Italian adult population”

“Surveillance of cardiovascular diseases in the Italian adult population”

“High-Tech activities in emerging countries: A network Perspectives of the Argentinean Biotech Activity”

“The Three-dimensional Substrate of Atrial Fibrillation in the Goat”

Atrial fibrillation (AF) is the most common arrhythmia in humans and Maastricht is a reference center for mapping of AF. Mapping is a technique to visualize the electrical activity of the atrial muscle. In earlier studies this was performed solely on the outer (epicardial) surface of the atrium. In this thesis we describe a novel technique and findings of simultaneous, endo-epicardial mapping. We could show that, while electrical activity during normal rhythm is synchronous at the inside and the outside of the atrium, it is getting increasingly dissociated if AF is present for a longer time (weeks to months). Along with this we could demonstrate that so called breakthrough events, that represent focal activations in two-dimensional mapping, are explainable by transmurally propagated electrical activity from the opposing side of the atrial wall in most cases. These findings help to understand what makes AF increasingly stable and harder to treat over time.

Key words:

atrial fibrillation, mapping, endo-epicardial dissociation

“Transcutaneous electrical nerve stimulation for patients with chronic pain”

“Learning in Urology; the influence of simulators and human factors”

“The dynamics of production in advance; three essays in how pre-made decisions on inventory can influence revenue-maximization and the nature of competition”

“Where the drug meets the road: actual driving, psychomotor performance and roadside drug screening methods in cannabis and ecstasy users”

Driving under the influence of drugs can affect the driving ability. This dissertation studies the interface between road safety and the use of ecstasy and cannabis.  THC (the active substance in cannabis) in the form of pills and the combination of lack of sleep and ecstasy appeared to negatively influence the driving ability. The ‘Standardized Field Sobriety Tests’ that are used on the roadside in North America to show decreased driving ability as a result of alcohol use, turned out insensitive to this form of THC. Saliva testing appeared not 100% suitable for reliable detection of THC, but this method has strongly improved over the last few years and appears promising for the screening of drivers for drug use.  

Key words:

drugs, driving ability, saliva testing, Standardized Field Sobriety Tests

“Diacylglycerol: an innocent bystander in skeletal muscle insulin resistance?”

Overweight involves fat accumulation in muscles and this phenomenon is associated with the development of insulin resistance, the pre-stage of type 2 diabetes. This dissertation studies the molecular mechanisms of fat induced insulin resistance, with particular attention to the role of diacylglycerol in this process. Diacylglycerol is a side-product of fat metabolism that accumulates in the muscle when the balance between fat absorption and fat burning is disturbed.   Using various research models (nutritional, pharmacological and genetic interventions) in test animals and persons the fat metabolism in the muscle is modified to analyse the role of diacylglycerol in insulin resistance of the muscle. One of the conclusions is that this cannot be explained by merely taking into account the quantity of diacylglycerol that is accumulated.

Key words:

overweight, insulin resistance, fat metabolism, diacylglycerol

“Economic consequences of public oversight of the audit market”

“Alcohol Consumption in Relation to Cardiovascular Risk and Mortality”

It is known that drinking alcohol in moderation is associated with reduced cardiovascular disease and total mortality in healthy subjects, whereas its abuse is unquestionably harmful. This thesis has confirmed previous studies in healthy people and has extended them to the association of alcohol consumption with cardiovascular and total mortality in cardiovascular patients. Highly sophisticated statistical analyses have been used to dissect the issue. In both healthy subjects and cardiovascular patients, teetotalers and heavy drinkers are at the highest risk whereas light-moderate drinkers are at the lowest risk. A similar relationship was found when either wine or beer consumption were considered. In conclusions: there is no reason to discourage either healthy persons or cardiovascular patients, if they are regular light-moderate alcohol consumers from continuing. Heavy or binge drinkers should always be urged to cut and modify their consumption.

Key words:

alcohol, cardiovascular disease, risks

“Interventional therapy in complex regional pain syndrome type 1: Predicting the outcome”

“Connecting the dots; new perspectives on stress and psychosis”

Psychotic disorders, among which schizophrenia, belong to the most paralyzing and elusive psychiatric diseases. Although it is assumed that stress plays an important role in the development of psychotic experiences, by far not everyone becomes psychotic after a stressful event. This dissertation studies why one person does and the other doesn’t react psychotically to stress – which mechanisms are involved there? One of the conclusions is that dopamine stress handling in the brains of persons with psychotic vulnerability shows defects – a defect that is partly ‘family-related’, but on the other hand may be stirred up by repeated exposure to radical stressful events.  

Key words:

psychotic disorder, schizophrenia, stress, dopamine

“Human Thermoregulation; A synergy between physiology and mathematical modeling”

This dissertation studies the regulation of the body temperature in both young and old people. Both the skin blood flow (regulation and heat release) and the energy use (heat production) were studied in a cool environment. In old people the core temperature went down, in contrast to the young people. There was, however, no difference in the change of the skin blood flow. On the other hand, young people increased the heat production, whereas that decreased in the elderly. Also, the blood pressure increased three times as much in the elderly as it did in the young people. The newly developed mathematical model shows that the decrease of heat production in the elderly is caused by cooling of the body. As opposed to young people, elderly people lose the capacity to compensate this decrease.

Key words:

body temperature, mathematical models, metabolism, skin blood flow