“The Pre-assessment Learning Effects of Consequential Assessment Modelling how the Examination Game is Played”

Exams can drive students to learn in undesirable ways, like memorising rather than trying to understand work. While this phenomenon has been researched extensively, research has not yet yielded a validated model to explain this behaviour. This dissertation proposes, and starts the process of validation of, a model that describes and explains students’ reactions to assessment. Validation is crucial because it allows the model to be used with greater confidence in a range of settings. These findings could help lecturers who develop assessments to understand how different assessment methods, and the way they are used, influence student learning. They could also enhance research about assessment as a tool to augment learning.

Key words:

learning effects of assessment, model, model validation, assessment, learning, mechanism of impact, determinants of action

“New horizons in nonpolypoid colorectal carcinogenesis”

Tracing and removing colon polyps during internal examination can stop the development of colorectal cancer at an early stage. Therefore, in the Netherlands from 2013 on the population older than 55 years will be screened. Recent research, however, shows that the preventive effect of colon examination is considerably less in the right part of the colon. A possible explanation is the contribution of so-called flat colon polyps. This type of colon polyps is more difficult to identify and remove and possible also of a more aggressive nature. This dissertation about the clinical and molecular characteristics of flat colon polyps shows that they make a larger contribution to the development of colorectal cancer in the right than in the left part of the colon. Adequate tracing of flat colon polyps therefore appears a condition for effective population screening for colorectal cancer.

Key words:

colon polyps, colorectal cancer

“Reactivity, recruitment and remodeling of collateral arteries in diabetes”

Diabetes (suikerziekte) verhoogt het risico op perifeer vaatlijden, een ziekte die het gevolg is van slagaderverkalking in de benen, en leidt tot verminderde mobiliteit en meer kans op voetwonden en amputatie. In dit proefschrift wordt arteriogenese beschreven, een natuurlijk proces waarin kleine bloedvaatjes (collateralen) groter worden om doorbloeding te herstellen. In een diermodel laten wij zien dat diabetes leidt tot verstoorde arteriogenese. Ook tonen wij in geïsoleerde vaatjes aan dat diabetes de vaatverwijding bemoeilijkt. Toediening van een vaatverwijdend geneesmiddel stimuleerde arteriogenese in het been in proefdieren. Deze geneesmiddeltoediening zou een veilige en effectieve behandelstrategie voor diabetespatiënten met perifeer vaatlijden kunnen zijn.

Key words:

Diabetes, peripheral arterial disease, arteriogenesis, collaterals, vasodilatation

“De veranderende wereld van de Medische Microbiologie”

“Support of an Asthma/COPD service for General Practitioners in daily care”

An asthma/COPD service supports the General Practitioner with the complicated diagnostics of asthma/COPD by performing lung function measurements, which lung specialist consultants subsequently assess together with a filled out questionnaire.  Research into the quality of the asthma/COPD service shows that this diagnostic procedure ‘on paper’ is reliable and just as good as a ‘live’ assessment in the lung specialist’s consulting room. The asthma/COPD service signals misdiagnosis and overtreatment in patients that use medication even before the diagnose is made.  Making the right diagnoses and additional advising with these and other diagnostic problems makes the asthma/COPD service a valuable diagnostic provision for General Practitioners and their patients.

Key words:

asthma/COPD diagnostics, cooperation primary care, misdiagnosis

“Nodal isolated tumor cells and micrometastases in early stage breast cancer”

Metastases in the lymph glands also determine the prognosis of breast cancer. 15 years ago, the sentinel lymph gland procedure was introduced, where only a limited number of lymph glands is removed from the armpits and examined for the presence of metastases. With this procedure, small metastases, i.e. isolated tumour cells (smaller than or equal to 0.2 mm) or micrometastases (0.2 – 2 mm) are often found in the sentinel glands. The prognostic value of such small metastases in breast cancer is currently questioned. This dissertation describes a national cohort study that shows that small metastases negatively influence the prognosis. In patients that underwent chemotherapy or hormone therapy the prognosis was better.  Therefore, these treatments should be considered with the presence of small metastases. Also the cancer did not return as quickly in the case of complete removal of the armpit glands. The dissertation also describes the role of the extensiveness and localisation of small metastases in the lymph gland and cost effectiveness aspects of the treatment.

Key words:

breast cancer, prognosis, isolated tumour cells and micrometastases

“Het kind van de rekening”

“The Politeness of Data Protection; exploring a legal Instrument to regulate medical research using genetic information and biobanking”

“The influence of adult education on the increase of Social inclusion”

Adult education can be a lever for increase of social inclusion among vulnerable adults. This thesis contains a series of studies concerning the outcome of lifelong learning programs among vulnerable adults. Some learners (circa half of the total population) undergo a ‘transition’ to better social inclusion after joining these programs, especially on four conceptions of social inclusion: activation, internalisation, participation and connection. The research results underline the importance of the variable transfer possibilities (referring to the possibilities one has to use the learned knowledge, skills and attitude in daily life) influencing the learning success among these learners. Further analysis show that not only elements of the learning environment influence the rate of increase of social inclusion. Especially foreign learners and people who live together without being married experience a higher rate of increase on several variables of social inclusion. Future research and the use of insights of the results of our study can stimulate professionals and researchers of lifelong learning to improve the learning environment of lifelong learning in adult education centres. The research is now continued in eight European countries, 87 communities and among 5500 learners.

Key words:

adult education, social inclusion, variable transfer possibilities

“Primary vascular access for hemodialysis treatment”

A well functioning vascular access is necessary for successful hemodialysis treatment (a therapy that replaces the kidney function). Vascular access can be created with an arteriovenous fistula (AVF), a connection between a coronary artery and a vein. The risk of treatment failure increases, however, if the patient has small or bad vessels. In that case an arteriovenous graft (AVG), an artificial blood vessel that is subcutaneously attached between a coronary artery and a vein, can be a solution. Research in this dissertation shows that, looking at the life span, patients with bad vessels indeed benefit from placing an artificial AVG as vascular access for dialysis.

Key words:

kidney failure, hemodialysis, vascular access

“MicroRNAs in the heart: micromanagers and sentinels of cardiac disease”

MicroRNAs are small molecules that have a great influence on a wide scale of cell functions and diseases.  This dissertation describes the role of microRNAs in heart diseases and the involvement of individual microRNAs in inflammation of the heart. Manipulation of such microRNAs leads to protection of or, on the contrary, a higher sensitivity of the heart to high blood pressure or viruses.  Also the ‘leaking’ of microRNAs from heart muscle cells during acute heart diseases can be measured in the blood which contributes to a quick diagnosis. Combined, these studies imply that microRNAs can be used for future treatments and diagnostic tests for cardiovascular diseases.

Key words:

MicroRNA's, heart diseases, inflammation of the heart

“Functional Cortical Cartography”

My research has focused on understanding the relationship between structure and function in the human brain. Just like fingerprints, each person has a unique folding pattern in their brain. This convoluted folding pattern is surely part of what makes us individuals, but also introduces some difficulties into the field of neuroimaging. First among these difficulties is the challenge of ensuring you can compare the same brain area across a population of subjects. By using advanced analysis techniques I was able to create probabilistic maps of function brain areas, allowing one to predict the function of a particular brain area, only by knowing its anatomical location. Furthermore, I developed new analysis techniques to improve the effectiveness of group brain imaging studies. Finally, I used these new techniques to track the development of the brain’s auditory system, in structure and function, through childhood, adolescence and into adulthood.

Key words:

human brain, folding pattern, neuroimaging

“Ik denk dus ik leer”

“Waterveiligheid: Managen van kwetsbaarheid voorbij de mythe van droge voeten; De Nederlandse omgang met overstromingdreiging in sociaal-cultureel perspectief”

This dissertation explains why flood risk is not an item in the Netherlands. After problems with rivers in 1993 and 1995, the Dutch government decided to stimulate public communication on water safety and public participation in water safety projects.  This would increase the water awareness of citizens and enhance risk-conscious behaviour. Research now shows the unexpected and undesirable side-effects of this policy: indignation, apathy and loss of public trust. According to Heems and Kothuis, the ‘safety myth of dry feet’ is the cause of the failing government policy: knowing that there is no absolute guarantee, but at the same time believing that the Delta Works guarantee dry feet.  Denying this widespread myth is necessary for social anchoring of the desired attitude towards water safety.

Key words:

water safety, communication, participation, safety myth

“Neuroinflammation as a cause of chronic pain”

“Participatory Ethnography of HIV/AIDS in Cartagena, Colombia: A Collective Analysis for Social Action toward HIV Prevention”

In order to address the local HIV/AIDS epidemic in Cartagena (Colombia), priority should be given to structural actions such as reducing socioeconomic inequalities, providing access to health care and education as well as regulations to prevent sexual exploitation and sexual abuse in the frame of sexual tourism. Among the actors that need to generate these large-scale structural changes are the government and private sector (e.g. national and international health insurance companies operating in Colombia and the international tourism industry).This proposal for HIV prevention and a collective analysis of HIV infection are the outcome of a five-year participatory ethnography conducted with 96 inhabitants of Cartagena. The collective analysis of HIV infection is summarized in a so-called ‘Local-Scientific diagram’, which pictures HIV infection in Cartagena as a social phenomenon that involves complex and dynamic interactions between local ideas of body, ethnicity, class, gender roles, sexuality, sexual risk and the social exclusion that derives from these interpretations. The diagram also sheds light on the way local dynamics of the government’s performance and the international sex tourist industry play a role in this complex social phenomenon.

Key words:

HIV/AIDS, Cartagena-Colombia, Participatory Ethnography, Structural actions, HIV-prevention

“Young onset dementia; characteristics and impact”

In the Needs in Young onset Dementia (NeedYD) study, 215 young people with dementia (started before their 65th) and their family members were studied for two years.  It turned out that for this group it took longer to diagnose dementia than for older people.  In 45%, before another diagnosis was made, such as psychological problems. Often, there was much distress before the diagnosis, such as family conflicts or work-related problems.  Moreover, the disease insight turned out higher in young than in older persons with Alzheimer’s disease (AD). Also behaviour problems appeared to occur less frequently in this group. The study shows that timely indication and diagnosis are important for this group and offer leads for the support of young people with dementia and their families.

Key words:

dementia at young age, diagnostics, clinical characteristics, impact

“In Search of a New Past: European Integration in a Historical Perspective”

“Clinical implications of idiopathic atrial fibrillation”

Young and seemingly healthy patients with atrial fibrillation should be better examined and supported, because this heart rhythm disorder is a possible lead for concealed cardiovascular diseases. In idiopathic atrial fibrillation, the heart beats fast and irregularly without a demonstrable cause.  Long-term research into a group of young and healthy people with idiopathic atrial fibrillation shows that often beginning cardiovascular diseases are present in these patients, or will develop within five years.  The dissertation shows that the findings for this group clearly differ from the control group of persons without heart rhythm disorder. Tackling the underlying problems at an early stage could reduce the risk of serious consequences of cardiovascular diseases later in life.

Key words:

idiopatic atrial fibrillation, cardiovascular diseases, echocardiography

“Rolandic epilepsy, unraveling benign”

Many children with epilepsy have Rolandic epilepsy, which mostly occurs during the night.  Earlier, it was often assumed that this epilepsy was benign and therefore needs little treatment. Now, however, it turns out that children with this type of epilepsy have more problems with language and reading than healthy children. These problems often already manifest themselves before the epilepsy is diagnosed. The cerebral cortex of children with Rolandic epilepsy appears, particularly in the left ‘language’ half of the brain, thinner than in healthy children. That difference seems to increase as these children grow older. Also, these children have deviating neuronal connections in the brains. All this makes Rolandic epilepsy much less benign than assumed.

Key words:

Rolandic epilepsy, children, language problems

“Experimentele Neurochirurgie: een visie op de toekomst”

“Lokaal integraal gezondheidsbeleid: realistische uitdaging of utopie?”

The importance of an integral health policy, also called ‘Health in All Policies’, is (inter)nationally emphasized. Intersectoral cooperation is a prerequisite to achieve integral policy. However, locally few initiatives are taken to intersectoral cooperation. This dissertation examines the possibilities of working internally within a municipal organisation on a coherent health policy, in general and more specifically for overweight.  Important elements are: how do you place health properly on the agenda of the local authorities, especially of officials who are not responsible for health issues? Can a Community Health Service stimulate municipalities to create a broader view on health? The research shows that for stimulating intersectoral cooperation concerning health problems commitment and dedication are required on all hierarchic levels in a municipality. Integral policy development needs administrative attention from the entire City Council, decisive direction at management level from the municipality, room in the policy process and competent Community Health Service professionals.

Key words:

Health in All Policies, integral health policy, intersectoral cooperation

“Corruption: A Violation of Human Rights and a Crime Under International Law?”

“De dominee en de tweede apostel Paulus”

“Less than meets the eye: The functional relevance of early Visual cortex across the visual domain”

In a series of areas in the human brains, among which the cerebral cortex, the visual perception is processed.  The ‘early visual cortex’ is the area in the cerebral cortex where the visual information first enters. This dissertation reports a study in which the normal brain activity in the early visual cortex is temporarily and locally suppressed by means of Transcranial Magnetic Stimulation (TMS). This temporary suppression turns out to limit the recognition and awareness of visual information, the visual short-term memory and the influencing of behaviour on the basis of visual perception.  This proves that the early virtual cortex does not play a specific role in visual perception, but that it is involved in several aspects of visual perception.

Key words:

Transcranial Magnetic Stimulation (TMS), visual perception, early visual cortex, visual short-term memory, priming

“Connecting hemosysis and visceral injury during cardiovascular surgery; studies on the causes, effects, and treatment of hemolysis-induced organ injury”

Patients who undergo major cardiovascular surgery run a relatively high risk of postoperative complications, such as intestine and kidney damage. This dissertation describes the connection between red blood cell injury (hemolysis), which is often the consequence of the heart-lung machine and blood transfusions during surgery, and the development of intestine and kidney injury after the operation. The various studies gathered in this dissertation show that patients that experience more hemolysis also develop more intestine and kidney injury.  Because it is possible to treat the consequences of hemolysis, the results of this dissertation can contribute to the prevention of complications after cardiovascular surgery.

Key words:

hemolysis, cardiovascular surgery, blood transfusion, intestine, kidney

“Bugs versus Humans: genomics translated into Public Health”

“Protein biomarkers in chronic disease. Proteomics-driven discovery”

For this dissertation proteomics techniques were used to find new/better biomarkers for aneurisms of the abdominal aorta (AAA), Multiple Sclerosis (MS) and the quality of donor kidneys. It is shown that certain proteins in the blood are associated with AAA size and growth, and can be helpful in determining a successful surgical intervention to treat the AAA. Moreover, in the perfusion liquid of donor kidneys proteins were found that are an indication for the vital strength of the transplant and the degree of protein glycation in the cerebrospinal liquid, which can play a role in unravelling the development of MS.

Key words:

Biomarkers, Proteomics, abdominaal aorta aneurysma (AAA), Multiple Sclerose (MS), Donornieren

“Motivating smokers to quit; Effectiveness and feasibility of a web-based multiple tailored smoking cessation programme and tailored counselling by practice nurses”

Smoking is worldwide the main avoidable cause of disease and early death.  A cessation advice by the general practitioner can help smokers quit smoking. However, due to lack of time GP’s are forced to take other measures. This dissertation shows the successful integration of fully automated online tailored counselling in the general practice: the smoking patient receives a personal cessation advice on the basis of a questionnaire he/she filled out. This appears to be (cost) effective. This method also turned out successful for reaching lower educated smokers, which is less successful via mass media. The dissertation also makes recommendations for improvements of the online tailored counselling, so that this programme can in the future be used via all general practices in the Netherlands.

Key words:

smoking cessation, online, general practice, effects, costs

“Functional added value of microprocessor-controlled prosthetic knee joints”

“Distributional Impacts of Public Policies; Essays in Ex-Ante and Ex-Post Evaluation”

This PhD thesis is a series of essays on disparities in healthcare use in Luxembourg, as well as poverty and inequality effects of cash transfers to families in Lithuania. In light of the ever increasing pressures on national budgets, finding efficient and effective public policies is a major challenge – both politically and research wise. For example, diverse and up-to-date information sources must be analysed, using appropriate policy tools, such as national tax-benefit microsimulation models – so that time relevant policy evaluations are made. Furthermore, most public policies, as well as their impacts, are highly national contexts specific. This has ensuing implications for an exchange of “good practices” across the countries.

Key words:

microsimulation, poverty and inequality, disparities in healthcare use, cash transfers to families

“Modern insights in foam sclerotherapy for varicose veins”

“Glaucoma Management; Economic evaluations based on a patient level simulation model”

Intensive intraocular pressure reduction can prevent blindness from glaucoma. While effective in some patients, it may be unnecessarily intensive in other patients, leading to a burden on quality of life and general health care consumption. It is hard to tell in advance which scenario will apply to a particular patient. This dissertation describes how a simulation model for disease progression was used to evaluate intensive glaucoma treatment in terms of long term health and economic consequences. It also describes the evaluation of a method to assess the potential value of implementing more personalized care in glaucoma.

Key words:

glaucoma, ocular hypertension,  economic evaluation, personalized care, health care efficiency, patient  level simulation.

“It has been done elsewhere, it can be done elsewhere: Impact of smoke-free legislation on smoking”

Many countries implement smoke-free legislation to protect non-smokers against the harm of second-hand smoke. In this dissertation, the implementation of smoke-free hospitality industry legislation in the Netherlands is studied. The Netherlands was compared with other European countries using the International Tobacco Control Policy Evaluation Project (ITC Project). The research shows that smoke-free legislation can stimulate people to quit smoking. Public support for smoke-free legislation is a condition for success. In the Netherlands, the implementation of smoke-free hospitality industry legislation was less successful than in other countries. The new government is advised to implement comprehensive smoke-free hospitality industry legislation and to run an educational campaign about second-hand smoke to increase public support for this policy.

Key words:

smoking ban, smoke-free hospitality industry legislation, smoking cessation, tobacco control

“Apathy in Alzheimer’s and Parkinson’s disease: Assessment, pathophysiology and treatment”

“Childhood and Adolescent Depression: The Role of Environmental Adversities, of the Serotonin Transporter Gene and of their Interaction, in a Development Perspective”

This research is based upon reasonable evidence that the environment moderates behavioural effects of biological systems (serotonergic neurotransmission) involved in the development of juvenile affective symptoms. The data suggest that the Serotonin Transporter gene is a genetic substrate for youth internalizing behaviour: adolescents who carry a less functioning variant of this gene have a greater risk to develop depressive symptoms when exposed to environmental adversities. This gene also plays an important role in determining the continuity/discontinuity of depressive traits throughout adolescence, thus confirming the theory that carriers of the less efficient allele have more negative feelings (about themselves and the world), which could turn into depression when under stress. Primary prevention strategies, promoting proactive and adaptive coping behaviours may reduce the likelihood of persistence of behavioural problems from early- to late-adolescence and, perhaps, to early adult years.

Key words:

Adolescence; Depression; Serotonin Transporter Gene; Adversities

“Mens rea and defences in European criminal law”

“Caveolin-1 and CD40L-CD40-TRAF interactions in vascular and metabolic disease”

Inflammatory and metabolic disease, such as atherosclerosis and obesity, are the main causes of morbidity and mortality in western societies. In this thesis we show that loss of certain cell structures called caveolin-1, which are important in lipid transport, protects against the initiation and progression of atherosclerosis and that hematopoietic specific loss of caveolin-1 leads to an anti-inflammatory state. Furthermore, we establish an important function for the pro-inflammatory CD40L-CD40-TRAF signaling cascade in atherosclerosis as well as in obesity.  We provide strong evidence that a precise intervention in Caveolin-1 biology and CD40L-CD40-TRAF signaling harbors the potential to develop new therapeutic agents to treat inflammatory disease.

Key words:

atherosclerosis, obesity, metabolic syndrome, caveolin-1, CD40L-CD40-TRAF

“The glycation pathway in type 2 diabetes and cardiovascular disease”

The increased formation of glycated proteins (advanced glycation end products (AGE’s)) is a possible mechanism to explain the increased risk of cardiovascular diseases with diabetes. Although earlier (animal) experimental studies have shown this role of AGE’s, research for this dissertation does not establish a connection between AGE’s in the blood and cardiovascular diseases in persons with diabetes type 2. Moreover, there is no definite epidemiologic proof for favourable effects of specific AGE-inhibiting treatments and for decreasing AGE’s in blood by existing treatments. This does not mean that AGE’s are unimportant in the development of diabetes 2 related cardiovascular diseases, but it does mean that the current biomarkers in blood don’t sufficiently reflect damage in tissues as a result of AGE’s. Better biomarkers are therefore needed.

Trefwoorden:

hart- en vaatziekten, diabetes type 2, versuikerde eiwitten, biomarkers

“Assessment of inflammatory activity in sarcoidosis”

Sarcoidosis is a disease that involves the development of spontaneous inflammations in various organs and tissues of the body.  Knowing whether the disease is active is important for the determination of the prognosis and the choice of treatment. In inflammatory diseases the glucose intake of the body can be increased. By labelling glucose radioactive, a PET scan can make an increased glucose intake visible and thus distinguish an active from an expired disease. However, this type of heavy and costly examination is not always necessary. PET scan examination, on the other hand, does appear to have a clear added value when complaints cannot be explained by lung function examination, X-rays and blood tests.  Also, the PET scan appears helpful with the determination of the extent of the disease. Choosing the right tests to trace active sarcoidosis can limit the burden for patients and help to keep the health care expenses affordable.

Key words:

sarcoidosis, activity, treatment, PET, costs

“Systematic reviews: from Archie Cochrane to Zefram Cochrane”

“Development and application of toxicogenomic-based biomarkers of immunotoxic and genotoxic exposure in European neonates”

Exposure in the womb to toxic substances originating from the mother’s nutrition and environment can lead to changes in the gene expression in the unborn child with possible damaging effects for the child. The research described in this dissertation identified such genes. The found genes provide indications of the way exposure to damaging substances can lead to an increased risk of cancer and a less functioning immune system. Moreover, it became clear that boys and girls react differently to toxic substances, which can be associated with gender-specific risks of cancer and immune-related disorders in youth.

“What counts? Cognitive development and arithmetical performance: the role of child- and environment-related factors”

Knowledge about the influence both the child and the environment have on the development of arithmetical skills is important for the realization of optimal development possibilities for each child. This dissertation describes the role that various child- and environment-related factors play in the development of arithmetical skills and underlying cognitive skills, such as work memory. Particularly studied are children at the age of four to eight years. It is also investigated if training at preschool age can stimulate specific cognitive skills. This dissertation provides insight that can among others support early monitoring and the approach of arithmetical problems and underlying cognitive problems.

“Multipathology in dementia: correlations with clinical diagnoses”

Dit onderzoek is gericht op patiënten met dementie die in hun dagelijks leven worden belemmerd door cognitieve beperkingen, vanuit een neuropathologisch standpunt. Voor dit onderzoek werden de hersenen van overleden dementiepatiënten gebruikt. De gevonden pathologie bevestigt de huidige classificatie van subtypes van dementie (o.a. ziekte van Alzheimer, vasculaire dementie, Lewy-body-dementie). Het belangrijkste doel van het onderzoek was een correlatie te vinden tussen het klinische beeld van de patiënt en de neuropathologische bevindingen na autopsie op de hersenen. Er werd een hoge prevalentie van comorbiditeit van verschillende pathologieën gevonden. Dit stelt de gangbare wetenschappelijke classificatie aan de kaak, waarin de predominante pathologie als de belangrijkste wordt beschouwd. Dit vraagt om een nieuwe multidimensionele benadering van dementie, waarbij dementie wordt beschouwd als een syndroom met een spectrum van symptomen en neuropathologische resultaten.

Key words:

Brain Bank, Alzheimer´s disease, vascular dementia, neuropathology

“Utility reforms and performance of the urban water sector in Africa”

“Neural substrates of skilled vision: Perceptual learning induces behaviourally relevant plasticity in human V1”

“Fatty acid handling and impaired glucose metabolism : the role of the renin-angiotensin system”

To prevent a worldwide epidemic of diabetes type 2, insight in the causes is necessary.  Diabetes is a disease where the body can no longer keep the sugar level within the normal boundaries. It is assumed that disturbances in the fat metabolism contribute to this. A disturbance between the supply of fats in the blood stream and the fat metabolism in the skeleton muscle (for example the burning of fats) can lead to fat clutters in the muscle which leads to insulin resistance. Research for this dissertation shows that the fat metabolism in the skeleton muscles is indeed disturbed in people with an increased risk of diabetes. The medicine Valsartan that lowers blood pressure turns out to improve these disturbances. This research provides insight in the development of diabetes and contributes to the prevention of diabetes by means of medication. 

“Regulation of re-epithelialization and immune modulation by surfactant, surfactant protein A and transforming growth factor ß”

Early delivery occurs increasingly often and involves underdeveloped lungs. Normally, lungs mature in the womb, but in the case of early delivery the maturing process takes place outside this protective environment.  The most vulnerable infants receive at this stage so-called “surfactant therapy”, which facilitates the breathing, as well as mechanical respiration. However, applying therapies to these delicate lungs can unintentionally cause damage. This dissertation describes studies into the functions of the surfactant and shows that this therapy can keep inflammatory reactions within bounds. By means of a cell cultivation model that imitates the pulmonary alveoli, this dissertation shows also for the first time that surfactant has a positive influence on the wound recovery.

Key words:

early delivery, lung development, artificial respiration, surfactant, wound recovery, inflammation

“The affective response to CO2 in healthy volunteers: An instance of a primal emotion”

“Suicide trends and antidepressant prescription in Italy and Ticino Canton, Switzerland”

“Preeclampsia: cardiovascular health and renal function”

Cardiovascular diseases are death cause nr. 1 in women. Yet, few people know that a pregnancy can provide important information about this. During pregnancy women can develop high blood pressure or pregnancy toxaemia (preeclampsia). In later life, these women run a higher risk of developing cardiovascular diseases. The pregnancy can be regarded as a test for the own health. Outside the pregnancy, these women often have high blood pressure, overweight and insulin resistance. These risk factors can be influenced by a healthy lifestyle. Therefore, these women should be offered cardiovascular risk management after the delivery.

Key words:

cardiovascular diseases, pregnancy

“Enforcing Health and Safety Regulation; a comparative Economic Approach”

“Electrocortical maturation of healthy preterm infants: the feasibility of automated analysis”

“Improving the risk assessment of inherited breast and ovarian cancer: clinical significance of BRCA1/2 variants and risk modifiers”

Genetic screening of the BRCA1/2 genes is performed to members of families with early onset breast and/or ovarian cancer. Identification of the BRCA1/2-mutation carriers (at risk of early onset of breast and/or ovarian cancer and others in the case of male carriers) and non-carriers (which have the same risk as the general population) allows providing adequate clinical options to these individuals regarding cancer risk prevention and, eventually, prevention of transmission of the disease-causing variants to their offspring. However, accurate risk assessment is hampered by the difficulty to predict whether a woman will develop breast or ovarian cancer and the high number of variants of uncertain clinical significance identified during genetic screening, as it is not possible to determine if these are disease causing. This thesis compiles several studies that describe successful approaches for a more accurate cancer risk assessment of individuals from breast and/or ovarian cancer families.

Key words:

breast cancer, ovarian cancer, familiar cases, risk assessment, genetic variants

“Modulation of fat oxidation: nutritional and pharmacological approach”

Obesity occurs more and more often, both in adults and in children. Obesity increases the risk of developing, for example, diabetes, high blood pressure and cardiovascular diseases. To raise the effectiveness of programmes that are aimed at body weight loss and the prevention of diabetes, extra strategies are necessary. This dissertation presents the effects of two nutrition strategies (changing the type of sugar in nutrition and the use of green tea supplements) and a pharmacological strategy that influence the fat oxidation. Although lifestyle intervention should be the first step in regulating body weight and prevention from diabetes, this approach does not appear effective for everyone. Food supplements or pharmacological interventions can be useful additions to make lifestyle interventions more successful.

Key words:

obesity, fat oxidation, diabetes, nutrition

“Hospital-at-home for COPD exacerbations: Evaluation of a community-based early assisted discharge scheme”

COPD is a lung condition with temporary exacerbations that lead to hospitalization in 20% of the cases. To limit the unfavourable effects of these hospitalizations for both patients and society, studies were carried out to investigate if part of the treatment can take place at home with home care support. This research shows that both short-term and long-term there are no differences in health outcomes for the patient and also the costs are the same.  Many patients, in fact, prefer to be treated at home over hospitalization. Patients should therefore be allowed to choose whether they want to be treated in the hospital of undergo part of their treatment at home.

Key words:

COPD exacerbation, hospital care, home care

“The evaluation of normal and pathological bladder sensations”

Studies of bladder sensations are often invasive and therefore aggravating for patients with an overactive bladder.  Aim of this PhD research was the development of non-invasive methods and an understandable and applicable terminology to evaluate bladder sensations. In focus groups, a constant urine production was generated by a so-called ‘water load protocol’. This protocol, combined with a constant focus on the bladder, offers the possibility to evaluate in a non-invasive way the origin of the sensation of having to urinate, and to establish a clear and applicable terminology.  Also by keeping a sensation-related urination diary that contains a scale for the degree of the urge and the degree of bladder fullness, bladder sensations can be evaluated.

Key words:

Bladder sensations, 'water-load' protocol 

“Effects of Haemostatic Agents on Trauma Induced Bleeding”

“Assistive Technology in persons with cognitive deficits: Feasibility, usability and effectiveness”

“Evaluation in health care innovations in fibromyalgia”

“Life and death at the mucosal luminal interface: A new perspective on human intestinal ischemia/reperfusion”

Shortage of oxygen (ischemia) of the intestine is a potentially life threatening disorder. To gain more insight in the underlying causes our research group developed unique human intestinal ischemia/reperfusion (IR) models. Reperfusion is recovery of the blood supply to tissues that were earlier (partly) devoid of blood.  Grootjans discovered that the small intestine disposes of ingenious mechanisms to limit damage to the intestinal wall after short periods of IR. He also discovered that longer ischemia with reperfusion involves damage to the congenital defence of the intestine, which contributes to the development of complications of intestinal ischemia. Future studies now focus on the development of treatments that can reduce death by intestinal ischemia in the future.

Key words:

intestinal ischemia, causes, small intestine

“Broadcast and network optimization”

Ordering search results, network stability and routing on the Internet are applications of which the performance almost entirely depends of automated solution methods. This dissertation studies fundamental aspects of solution methods for these problems.  
The simplest solution methods that will always find the best solution is trying each possible solution one by one and selecting the best one. Even on the fastest computer this method takes too much time: years instead of days!  
Finding a solution method that is both fast and finds the best answer, appears unfortunately not always possible.  This dissertation describes solution methods that are very fast, but find a very good answer instead of the best answer. Moreover, for various problems better and simpler solution methods are described.

Key words:

automated solution methods, fundamental aspects

“Komt een psycholoog bij de dokter”

“Daily activity monitoring in patients with COPD; assessment of upper and lower extremity performance”

“The psychosocial determinants of sexual behaviours that place  traditionally initiated and circumcised young men in the Eastern Cape Province of South Africa at risk of STI/HIV’ infection”

“National Socialist Family Law; the influence of National Socialism on marriage and divorce law in Germany and the Netherlands”

To which extent has the marriage and divorce law in Germany and the Netherlands in the period 1933-1945 been influenced by the national socialist range of ideas?  To answer this question, extensive research has among others been conducted in the archives of the NIOD. The marriage and divorce law was used by the Nazis to build their Thousand Year Aryan Reich. For this purpose, many Aryan children and as few as possible half-Jewish children had to be born. Therefore, the Nazis, both in Germany and the Netherlands, tried to change the rules regarding marriage and divorce, among others forbidding marriages between Aryans and Jews. Also the divorce law was liberalized, allowing marriages in which it was unlikely that children would still be born, to be dissolved more easily. However, the final conclusion is that the Nazis indeed made many changes in the marriage and divorce law, but that this law never became entirely national-socialist.

Key words:

family law, Second World War, divorce law

“The History of the Nederlandsche Cocaïne Fabriek and its Successors as Manufacturers of Narcotic Drugs, analysed from an International Perspective”

The aim of this research was to realize a detailed description and analysis of the history of the production of narcotic drugs in the Netherlands (1900-1995). The most important companies that produced these drugs were the Nederlandsche Cocaïne Fabriek (NCF) and its successors. It turned out that acquiring the vegetable resources at low cost and having access to sufficiently large domestic markets are requisites for commercial success.  Because there are no internationally standardized figures about the volume of the worldwide cocaine production before 1930, Bosman developed an estimation method. The research also proves hat recent statements by writer Conny Braam about enormous quantities of cocaine, delivered by NCF to warriors during the First World War entirely lack foundation. 

Key words:

cocaine, production, Netherlands, 20th century

“Explaining Sickness Absence Behaviours among Public School Teachers in the Eastern Cape Province, South Africa: a socio-psychological analysis”

“Ensuring the Competence of Dental Practitioners through the Development of a Workplace-based System of assessment”

“Learning from error to improve patient safety”

Errors in health care can lead to dangerous situations and harm the patient and must therefore be reduced to a minimum. This dissertation clarifies from various perspectives how learning from errors can improve patient safety. Studied were the types of errors that are made in hospitals, the perception of medical students about patient safety, the differences in perception between students, residents and specialists about what constitute medical errors, and the role of training in making students aware of what goes wrong around them. Despite the many possibilities in health care to learn from errors, there is mainly still ground to be gained in the field of culture change. Learning from errors should be dealt with more consciously by using more types of errors as a learning moment. Extra attention for the social factors that influence learning could prevent potential errors in the future.

Key words:

Patient safety, health care, learning from medical errors, training

“Doorzien en Ontrafelen”

“All roads to thrombus formation; demystifying platelet signaling pathways”

Blood platelets have a central role in the process of haemostasis (the process of making the bleeding stop in a damaged blood vessel wall) and thrombosis (clotting of a blood vessel). The latter can lead to blood vessel obstruction causing a heart infarct or a stroke. The current antithrombotic, anti-blood vessel medication is only partly effective, and an increased risk of bleeding often creates a considerable complication. For the development of personalized target-specific medication with fewer side-effects a more exact knowledge of the complex process of thrombus formation and mainly the involved blood vessel signalling pathways is essential. The insight described in this thesis is a contribution to future developments in the treatment of arterial thrombosis.

Key words:

Blood platelets, thrombus formation, signalling pathways

“Incentives and Behavior in Markets”

This dissertation studies incentives and behavior in four different markets, ranging from the effects of charity characteristics on their cost-effectiveness, to individuals' behavior in internet auctions. For instance, we show that bidders adapt their bidding strategies over time and point toward the possibility for an auctioneer to increase revenues by adapting its focus to attract novice bidders.
Second, we study the cost-effectiveness of charities and show that it significantly varies with a charities' funding structure. This has important implications for potential donors and can help them to avoid low performing charities.

Key words:

incentives en gedrag op markten

“Market integration through ‘network governance’: The role of European agencies and networks of regulators”

The institutional design of EU energy and telecoms regulation has evolved in the last two decades. Mechanisms to encourage cooperation between national regulators have progressively been established: first, loose networks of regulators, then enhanced networks of regulators and eventually stronger and more formal forms of coordination, through European agencies or other new institutional models. In the energy field, a true ‘networked’ European agency has been created: the Agency for the Cooperation of Energy Regulators (ACER). In telecoms, a two-tier institutional structure has been set up: the Body of European Regulators for Electronic Communications (BEREC) and the Office. The features of ACER and BEREC show the intention to institutionalise the existing networks of regulators and confer a higher status upon them, with a strengthened and recognised position in the EU. However, this process raises concerns of legitimacy and accountability.

Key words:

EU marktintegratie, Europese agentschappen, netwerken van regelgevers, ACER, BEREC

“Developmental Immunotoxicity Testing for Hazard Identification”

Children can be more sensitive to chemical substances than adults. However, in the current safety evaluation of chemical substances, the specific sensitivity of children is possibly not sufficiently taken into account. This dissertation has established by means of animal studies that the developing immune system during the pre- and post-natal phase is relatively sensitive compared to general parameters of growth and development. The results have contributed to the development of a new international test directive for a generation study with additional immune parameters, which may enable better protection of children against the possible harmful effects of chemical substances.

Key words:

developmental immunotoxicity, sensitivity in children, hazard identification of chemical substances

“La contribution du droit penal de l’environment a la repression des atteintes a l’environnement au Benin”

This study is an analytical and critical diagnosis of the penal system of protection of the current environment in Benin.
Benin, following the example of the other African countries, is confronted with a continuous degradation of the natural and environmental resources. Can the criminal law of the environment, just like the other legal disciplines, contribute effectively to the protection the aforementioned resources? This problem which underlays our research works raises certain number of legal concerns which determine the future of the criminal law of the environment.
The thesis concludes that in spite of the difficulties which mark out the implementation of the criminal law in the environmental protection, its effective application remains relevant.

Key words:

criminal law, environment, protection

“L’effectivité du droit à l’eau face au processus de libéralisation du secteur de l’eau en Afrique subsaharienne”

“Improving ventricular pacing in adults and children; to treat or to avoid dyssynchrony-induced cardiac failure”

This research shows that even patients with mild cardiac failure induced by dyssynchrony (a badly coordinated contraction of the heart) can benefit from ‘resynchronizing’ both heart chambers by artificial stimulation of both heart chambers.  In children and young adults for whom artificial stimulation of the heart chamber is necessary it is important to make sure that this artificial stimulation does not cause a deterioration of the heart function. The described studies show that the place where the heart is stimulated has an important influence on the heart function. 
The best heart function was witnessed in stimulation of the chamber that pumps the blood into the body. This research contributes to the improvement of pacemaker therapy in adults and children for the treatment or prevention of heart failure induced by dyssynchrony.

Key words:

dyssynchrony, cardiac failure, pacemaker, heart function

“Factors influencing implementation of nutritional intervention in elderly subjects after hip fracture”

Elderly persons with a hip fracture often lack appetite. This can delay the recovery. Therefore, a study was conducted in which elderly with a hip fracture received intensive nutritional coaching by a dietician (10 contact moments) during 3 months if necessary combined with fluid nutrition. This coaching took place both in the hospital and in recovery care and in home situation. 
To test the usability of this nutritional intervention in the health care practice a process evaluation was carried out. The provided nutritional intervention turned out well applicable and was highly appreciated by patients. However, introducing this intensive nutritional care requires extra attention, particularly due to the lack of structural attention for nutrition in the existing health care.

Key words:

nutritional care, hip fracture, dietician and fluid nutrition, process evaluation

“De social defeat-hypothese”

“Institutionalization of International Justice”

“MicroRNAs: small directors with crucial powers in heart failure”

“Iraanse vluchtelingen en asielzoekers in beeld: Ervaren begeleiding, psychopathologie en perceptie van kansen”

“Immune control by the autonomic nervous system: Towards clinical implementation of enriched enteral nutrition”

Implementation of enriched nutrition around an operation might reduce complications. This dissertation contains several studies that support this claim. Enriched nutrition in the intestine triggers a nervous reflex that inhibits the inflammatory reaction and protects various organs (among which the intestine).  Moreover, enriched nutrition appears effective when the body has already suffered damage, so that this treatment can also be applied to patients after an accident. It is also very important that enriched nutrition not only mitigates the acute and very intense inflammatory reaction, but also leads to a more effective immune system in the period afterwards.

Key words: 

enriched nutrition, intestine, nervus vagus, autonomic nervous system, inflammation, surgery

“Interorgan short chain fatty acids exchange in humans; implications for clinical application in colorectal surgery”

“Neurobiological factors modulating H1-antihistamine induced cognitive impairment”

Some anti-allergy drugs (antihistamines) can cause fatigue. In the treatment of hay fever this fatigue is undesirable, because it can increase the risk of car accidents. But in the treatment of, for example, sleep disorders this fatigue may actually be desirable. This dissertation studied which mechanisms in the body make certain anti-allergy drugs cause fatigue.  The research shows that genetic individual differences between people play a role in the degree of fatigue. The message of this dissertation is that these individual differences should be taken into account in medication treatments to guarantee the safety of treatments with among others antihistamines.

Key words:

Antihistamines, attention, healthy volunteers, MRI, EEC, driving studies, sedation/fatigue, cognition

“Effectiveness and cost-effectiveness of nutritional intervention in elderly subjects after hip fracture”

Malnutrition often occurs in the elderly. The department of Epidemiology of Maastricht University, in collaboration with the departments of Surgery, Orthopaedics and Dietetics of the Maastricht University Hospital, the Atrium Medical Centre and the Orbis Medical Centre, investigated the effects and costs of extra nutritional care in elderly with a hip fracture. During 3 months, the patients received intensive coaching by a dietician (10 contact moments), if necessary combined with fluid nutrition. This appeared to lead to an improvement of nutritional intake and nutritional state of the patients, but it had no effect on the duration of hospitalization or recovery care, nor on the number of complications or the functioning of the participants. The costs of this intensive nutritional care turned out remarkably low: average €600 per patient, which is only 3% of the total care costs per patient with a hip fracture (appr. € 23.000).

Key words:

malnutrition, hip fracture, nutritional intake

“Harvesting and validating experiental expertise to support autonomy of people with diabetes mellitus. In search for successful diabetes-related behaviors regarding driving and work”

For this dissertation professionals harvested and validated the experiential expertise of people with diabetes mellitus. By harvesting how this target group exactly deals with (in this case) driving a car and working, others, who don’t have this experiential expertise yet, can learn. The main factors appeared to be the ability to anticipate and react to hypo attacks during the drive, adequately informing and instructing passengers, anticipating problems during job interviews, executing effective self-management activities to prevent hypo and hyper attacks on the work floor, and successfully negotiating with employers about adaptations of the work circumstances.

Key words:

Diabetes mellitus, ervaringsdeskundigheid, autorijden, arbeid

“Essays on Monetary and Fiscal Policy in Good and Bad Times: Economic Theory and Econometric Methods”

“Cochlear Implantation; surgical and audiological assessment of cochlear implantation techniques”

“Prediction of Abdominal Aortic Aneurysm progression”

“Platelet-associated hypercoagulability in patients with Essential Thrombocythemia and Polycythemia Vera”

Thrombosis is a frequent complication in patients with cancer. In patients with hematological malignancies, such as Essential Thrombocythemia (ET) and Polycythemia Vera (PV), thrombotic events are a major cause of increased morbidity and mortality. The pathogenesis of the activation of blood coagulation in these patients is complex. Platelets have an important role in this process. This thesis presents studies exploring the platelet-associated hypercoagulability in patients with ET and PV. The acquired JAK2V617F mutation, which has been reported in nearly all patients with PV and in more than half of patients with ET has been associated with severity of disease and increased expression of soluble or cellular biomarkers of clotting system activation. This thesis confirmed a hypercoagulable state in patients positive for the JAK2V617F mutation, associated with the highest thrombin generation values.

Key words:

cancer and thrombosis, thrombin generation, platelets.

“Limiting viral infections with immunomodulating agents”

Viral infections occur often and they can cause serious health problems. Despite the success of the current antiviral drugs and vaccines, new medication is necessary.  In this dissertation, a series of experiments shows that specific drugs that can strengthen the immune system, are capable of protecting cells against viral infections. Here, particularly the substance interferon-beta turned out to play an important role. Moreover, it turned out that direct exposure of cells to interferon-beta led to long-term protection against a viral infection. These findings may be important for the future treatment of patients with an increased sensitivity to viral infections.

Key words: 

viral infections, health problems, interferon-beta, immunity stimulation 

“Tailoring conservative care in osteoarthritis”

This dissertation studied the care needs and treatment of people with advanced osteoarthritis. It turned out that people with osteoarthritis in several joints run a higher risk of developing serious complaints in pain, physical and psychological functioning. A feasibility study into the effectiveness of a treatment showed important differences in care needs between patients. In follow-up research this should be taken into account. It was also shown that approximately 25% of the people waiting for a new joint as a consequence of osteoarthritis deteriorate in pain and functioning. This can have negative consequences for the outcomes of the operation. For these people, the usefulness of an intensive therapeutic training prior to the surgery was investigated. Literature studies show that this type of training is not useful for young, fit persons. However, fragile, elderly persons possibly benefit from such training. Particularly this last group did not participate in the feasibility study, because they could not come to the hospital. In follow-up research, therefore, the practitioner will have to visit he patients.

Key words:

osteoarthritis, treatment, care needs

“Hybrid thoracoscopic epicardial and transvenous endocardial catheter ablation of atrial fibrillation”

“Let’s do drugs”

“From hiring to firing”

This dissertation describes, compares and analyzes policies of the United Nations Secretariat and the European Commission concerning staff appointment, placement and separation. It finds that recent reforms did not affect the existence of the concept of international civil service in these institutions, but that the emphasis has moved more towards ensuring a less costly and more flexible work force. While continuing to provide for a number of important legal safeguards for the independence and impartiality of staff, even improving the previous state of affairs in a number of areas, the study argues that the situation is not yet ideal. It recommends, for example, that the UN Secretariat revises its legal framework for ensuring adequate geographical representation and introduces better promotion and mobility frameworks. For the European Commission, the study calls for more transparency on de facto national quotas and for simplification of the legal framework concerning various types of appointment. The study also argues that proper procedures are needed for appointment of all, not merely some of, UN and EU staff.

Key words:

UN Secretariat policies, international civil service, workforce issues

“On the Productivity and Efficiency of Education - The Role of Innovations in Dutch Secondary Education”

Innovative schools in general perform better than less innovative schools. Moreover, this dissertation shows that Dutch schools for secondary education are relatively efficient (although there are major differences between schools) and that innovations, the distribution of financial means and scale play an important role in that. The efficiency scores of schools vary per region and school type. Finally, it turns out that about one fourth of the schools are still in the middle of a considerable improvement process. These conclusions contribute to the discussion about productivity and efficiency in secondary education and the role of innovations.

Key words:

secondary education, innovative schools

“The best of both worlds? Studies on Healthy Indulgences and Their Effects on Food Intake Control”

This dissertation investigates the effects of healthy indulgences (i.e., indulgent foods featuring front-of package claims such as “extra antioxidants”, “low-fat”, “reduced sugar”, or “with vitamins”) on consumers’ ability to control their food consumption. The research shows that exposure to indulgences carrying functional health claims (e.g., “with antioxidants”) leads to reduced consumption, whereas exposure to indulgences carrying hedonic health claims (e.g., “low-fat”) stimulates increased consumption relative to a regular food packaging featuring no claims. These findings have broad relevance to the food industry in that they highlight the negative repercussion of the currently popular strategy of offering healthier alternatives of inherently unhealthy foods, when the attributes the claims stress are of functional nature. For public policy makers, the findings might provide some comfort that not all marketing efforts aimed at promoting more wholesome alternatives of indulgent foods necessarily have negative consequences regarding consumers’ eating patterns; in that functional health claims potentially help consumers to control how much they eat.

Key words:

healthy indulgences, consumption, self-control

“Segmentation of Animations: Explaining the Effects on the Learning Process and Learning Outcomes”

Animations are more and more often used in instruction materials. Segmentation, presenting animations in parts with short breaks in between instead of one continuous stream of information, is one way of optimizing instructive animations for learning.  The studies described in this dissertation investigated why segmentation positively influences the learning process and learning outcomes. It was found that the breaks are important for the positive effects, but that showing how the information can be segmented into meaningful parts may also play a role in these effects. Furthermore it was found that segmentation of animations is only favourable for beginning learners.

Key words:

Animations, learning, instruction material design

“To condition or not – is that the question? An analysis of the effectiveness of conditionally and targeting in social cash transfer programs”

Social cash transfers have been identified as one interesting option in low-income countries to combat poverty. Whether the cash should come with any conditions attached has been controversially debated by academics and policy-makers. Drawing on uniquely designed experiments, survey and qualitative data, this dissertation critically analyses the appropriateness of conditionality for the low-income country context. Using Zambia as a case study, it discovers that conditionality proves not only to be a politically powerful tool but also to empower, rather than patronize beneficiaries. Conditionality, however, comes at a price: it excludes households from the program, foregoes poverty reduction effects, and overburdens the administration.

Key words:

social cash transfers, conditionality, low-income countries

“Nanotoxicology – an in vitro approach”

Nanotechnology is a technology that enables making and adjusting materials on a scale of one millionth millimetre. On this scale materials get other attributes that can be favourable, such as a more focused administration of a medicine to the target organ.  However, it is not known if there are risks attached to nanomaterials. Because of the large variety of nanomaterials it is not achievable to test each nanomaterial separately for possible risks. This dissertation presents methods that could – after further development - make the risk assessment of nanomaterials more efficient, such as the use of tests with cells instead of test animals, and the use of safety data of one nanomaterial for another nanomaterial.

Key words:

nanotechnology, risk assessment, nanomaterials, risk

“Clinical and Molecular genetic studies in the neurocutaneous and cutaneous porphyrias”

“Diffusion Weighted Magnetic Resonance Imaging: Validation, Correction and Applications”

Diffusion weighted Magnetic Resonance Imaging (DW-MRI) images the structure of the white substance in the brains and connections between various brain parts. To validate this technique a test object (phantom) was developed, the structure of which resembles the structure of the white substance. This phantom was brought on the market and by now over 15 universities and hospitals own one.
Furthermore, DW-MRI was applied to a patient with Landau-Kleffner syndrome. This syndrome involves losing the ability of using and understanding language as a consequence of epilepsy. Intensive therapy can restore the language ability. Important connections for language processing look different in these patients and the brains use more visual information in communication.  
The dissertation also describes further studies with a blindsight patient. In these patients the eyes still function, but the visual information is no longer consciously processed. And yet, the deep brain parts that unconsciously process emotions and visual information appear active. The necessary brain connections were shown in this patient and they were not present in control persons. Therefore, the patient has created new connections.

Key words:

Diffusion weighted MRI, Landau-Kleffner syndrome, blindsight

“Conditions of Peer Assessment for Complex Learning”

Peer assessment (assessing each others’ work) fits in with self-steered and cooperative learning by pupils. Moreover, it is an important professional skill.  Scientifically not much was known about its effectiveness and the degree to which pupils learn from it themselves. This dissertation studied peer assessment in high schools for Havo and Vwo. One of the conclusions is that when students have to assess each others’ work before they master the study subject, this method has a contrary effect. Therefore, it is recommended to support the pupils in this area with a step-by-step instruction. As the instruction progresses, and the knowledge and skills of the pupil increase, this support is gradually reduced.

Key words:

secondary education, peer assessment 

“Epidemiological and biological mechanisms of cannabis as cause of psychosis”

“Unemployment and employability: how firms can help”

This dissertation shows that companies can make a measurable and significant contribution to the reduction of unemployment and the stimulation of employability of low educated persons. For this purpose, three private initiatives of Philips were studied: the Philips Werkgelegenheidsplan (WGP/Philips Employment Plan), Certification of Skills, and E (mployability)-miles (E-miles).
The main conclusions are that a participant in the employment plan has an 18 percent bigger chance of finding a job than a comparable unemployed person who did not participate. This means that the impact of the employment plan is much more important than those of public re-entry tracks. Low educated people, who participated in the Certification of Skills track, averagely earn more afterwards, are promoted more often and less often dismissed than non-participants. Employees who make use of E-miles become more aware of the importance of personal development and training.

Key words:

private employment initiatives, reducing unemployment

“Bipolar disorder and cognitive functioning: A two-year naturalistic study”

Patients with a bipolar (manic-depressive) disorder suffer from extreme mood swings that take shape as depression and/or mania.  Bimonthly, a group of 76 patients was neuropsychologically examined over a period of two years. Studied were the course of their cognitive functioning by testing among others memory and attention functions and the influence of clinical variables on that, such as mood and medication. The cognitive functioning turned out to vary strongly over time and could only be partially explained by the mentioned variables. Medication used in the treatment of psychotic symptoms turned out to have the strongest negative effects on cognitive functioning.

Key words:

bipolaire stoornis, cognitief functioneren

“Talen in beweging”

“Pleiotropic effects of non-structural matrix proteins in the stressed heart. ECM remodeling in cardiotoxicity, aging and cardiac allograft rejection”

“De zoete inval”

“Back to reality. Exploring the phenomenology of psychosis in daily life”

“Drug-induced movement disorders in long-stay psychiatric patients; genetic and non-genetic risk factors: A prospective study”

On the site of a psychiatric hospital a man walks with a bent back, slowly with a shaking hand. What is the matter with him? This is one of the movement disorders caused by anti-psychotics. This dissertation shows that movement disorders occur often in this patient group and that therefore prevention is crucial. The hope that the new anti-psychotics would make these horrible side-effects disappear turns out an illusion. Older age and higher anti-psychicum dose are risk factors for certain movement disorders. Analyses of earlier studies suggest multiple genetic influences. Also in additional research weak genetic signals were found that ask for larger long-term random studies, in which the fluctuating course of movement disorders and gene-environment interactions can be included.

Key words:

bewegingsstoornissen, antipsychotica

“The structural plasticity of serotonergic and dopaminergic systems: a multidisciplinary approach”

“New pathophysiological concepts and potential therapeutic targets for oxidative phosforylation disorders”

Mitochondria are the power stations of a cell. The function of mitochondria can become disturbed by genetic defects in cell nucleus or mitochondrial DNA. These lead to a wide range of syndromes in which mainly brains, liver tissue and muscle tissue are affected.   To find out which disease processes are activated by their genetic defect, this PhD research developed a series of model systems, using cells or tissue from patients. The identified processes may be interesting for therapy. The current technological progress leads to a quicker increase of newly developed variants in both cell nucleus and mitochondrial DNA. Therefore, an analysis was made of the normal variant in the mitochondrial DNA of a large population that can improve the classification of new disease-causing variants. 

“Mechanism design and characterizing incentive compatability”

“Deep infiltrating endometriosis; environment, genetics, epigenetics”

“Morbidity and mortality risk of aging diabetic and psychogeriatric patients”

This dissertation studies the multi-morbidity (multiple disorders), functional impairments and frailty in diabetes patients. All patients that we examined had at least one co-morbid disorder. Eighty percent had more. We can conclude that in aging patients with diabetes the weight of care and the burden of the disease were considerable. The risk of repeated falling is 1.5 times higher in aging patients with diabetes than in aging people without diabetes. This is partly explained by medication, pain and loss of strength in the joints and muscles, a bad health and less physical activity, and cognitive disorders. Our findings show that an active lifestyle and fall prevention should be part of the treatment of all aging patients with diabetes. Screening for frailty turned out not useful.

Key words:

diabetes, multi-morbidity, functional impairments, vulnerability

“Europa, het bindweefsel van het hart”

“Self and other regarding motives in decision making under uncertainty”

“Why does Europe have a drinking problem”

“Econometric Methods for Financial Crises”​

“Is the gut the key to obesity? The involvement of the intestine in obesity, type 2 diabetes mellitus and fatty liver disease in man”

Worldwide, the increasing number of people with obesity and accompanying disorders such as diabetes and fatty liver disease is a considerable problem.  The studies gathered in this dissertation emphasize the role of the intestine both in obesity as in fatty liver disease. They showed for example that obese people have a specific composition of intestinal bacteria that involves local inflammation in the intestine and systemic inflammation that is measurable in the blood. Moreover, we found indications that people with overweight and diabetes have more small intestine cells. 
Finally, we studied fatty liver disease, a disorder that starts with relatively innocent liver fattening, but can lead to serious liver infection, liver failure and liver cancer. The blood of people with liver infection contains higher concentrations of antibodies against these bacterial products that occur in the intestine. We also found that the diagnostics of this fatty liver infection can be simplified by means of breath analysis.

Key words:

obesity, intestine, type 2 diabetes, fatty liver disease

“Tailoring Hemodialysis Vascular Acces. Preoperative imaging techniques and computational modeling”

For adequate hemodialysis, patients with terminal kidney failure are dependent on a well functioning   vascular access. In spite of extensive preoperative echo examination, frequent complications occur as a result of the fact that the vascular access is placed on a wrong location. This means a too high or too low blood flow.  
This dissertation describes three methods that can limit these complications:   1) extend the preoperative examination with a scan that visualizes all blood vessels in the arm as a whole, 2) conduct elasticity measurements of the blood vessels in the upper arm, and 3) the preoperative prediction of the height of the blood flow after the operation for vascular access at various locations in the arm by means of a computer simulation model.

Key words:

kidney failure, hemodialysis, vascular access

“(Epi-) Genetic Profiling of Colorectal Cancer: Prognostic and Biological Relevance, with emphasis on tumor hypoxia”

“De waarheid ten tonele: Harold Pinter over kunst, waarheid en politiek”

“Lobbying for the Ear. The Public Fascination with and Academic Legitimacy of the Sonification of Scientific Data”

“The endothelial glycocalyx in early atherogenesis. Roel in platelet adhesion?”

“Advanced glycation and type 1 diabetes”

This dissertation studies the connection between the glycation of proteins and type 1 diabetes-related complications, among which cardiovascular diseases.  Several determinants of the glycation of proteins were related to cardiovascular diseases in type 1 diabetes. The main conclusion is that the glycation of proteins is a mechanism that can lead to complications in type 1 diabetes. With the observed connections the research creates perspectives for prevention or treatment of type 1 diabetes-related complications.

Key words:

diabetes 1, glycated proteins, cardiovascular diseases

“Nobelprijs voor onderwijs?”

“Relocation, Mobility and Migration; the Dynamics of the Workers and Firms in the Netherlands”

“Pricing and Scheduling under Uncertainty”

“Can the University save Europe?”

“Effect of Flavonoids on Fetal Programming. Implications for Cancer Susceptibility”

Chronic diseases that occur at the adult age, such as cancer, threaten man’s health. The in utero period, the stage in the uterus, seems to play a role in the development of cancer and is among others determined by the mother’s nutrition. Mice that during pregnancy were exposed to flavonoids, nutrients with an antioxidant effect that are believed to protect against the development of cancer, turned out to be better protected against the development of cancer at an adult age. The reason was among others that their antioxidant defence system was increased.

Supervisor:

cancer, nutrition, uterus, antioxidants 

“Ultrasound Guidance for Interventional Pain Management of Cervical Pain Syndromes”

“Growing up getting drunk; development and prevention of adolescent alcohol use”

Alcohol use is the main cause of disease and death among adolescents in Europe. This is the first Dutch research that studied the effects of intensified enforcement of the age limits for alcohol use (formal control) and of making alcohol less available to adolescents via the social environment (informal control via parents and schools). Increasing the formal and informal control turned out to reduce the risk of intoxication in drinking adolescents. Given the upcoming decentralization of enforcement to municipalities, this means that the Dutch community must actively increase formal and informal control to reduce intoxication among adolescents.

Key words:

adolescent alcohol use, intoxication, enforcement, formal control, informal control

“Socioeconomic inequalities in health: Exploring new psychosocial pathways in middle-aged and older people”

Socioeconomic inequalities in health, i.e. inequalities in health between higher and lower educated people or between richer and poorer people, are an important problem worldwide. Unhealthy behaviour, which occurs more often in lower socioeconomic classes, only partly explains the inequalities. Growing up in unfavourable socioeconomic circumstances forms an individual. His personality, his coping styles and his social relations (psychosocial characteristics) are strongly influenced by the circumstances. This dissertation shows that an unfavourable psychosocial profile occurs more often in lower socioeconomic classes and this leads to greater unhealthiness, even at middle age and old age.

Key words:

socioeconomic inequalities in health, circumstances

“Quantitative assessment of sustainable development and growth in Sub-Saharan Africa”

The relatively weak performance of African countries compared to countries in other world regions in all development aspects (economic, social and environmental) suggests that these aspects are not independent. The central research question is: How are the different aspects of sustainable development inter-related? This thesis develops and applies diverse quantitative economic methods to comprehensively analyze the interdependencies between different aspects of development: living standards/income, education and health. The main finding is that there is a positive mutual reinforcement between education and health outcomes. Furthermore, decent education and good health are necessary conditions for economic development and, hence, for overall sustainable human development.

Key words:

Sub-Saharan Africa, quantitative economics, sustainable development

“Risk- and Social Preferences of Individual Investors”

This dissertation studied the behaviour of a large group of individual investors from Robeco, ASN Bank and Triodos Bank. The research shows that sustainable investors also behave more socially in other contexts than common investors. For example, sustainable investors donate substantially more money to charity, practice volunteer work more frequently, and are more often registered as organ donors. Moreover, the dissertation shows that there are two types of sustainable investors. A large group of investors buys sustainable funds because of their personal inclination to contribute to a better world. The other important group of investors buys sustainable funds for a financial reason, such as tax privilege or a higher expected return. And finally, the dissertation shows that sustainable banks, such as ASN Bank and Triodos Bank benefit from the loyalty of sustainable investors, because these investors not only think of Financial return, but also social return.

Key words:

behaviour, individual investors, sustainable

“Dominant Mothers, Queer Sons. (Un)doing Momism in Postwar American Culture”

“Big Boys Don’t Cry! Or Do They? Can forensic patients change?”

“Bacterial and fungal infections: evolving towards molecular pathogen diagnostics”

A quick diagnosis of infectious diseases can advance treatment efficiency, and thus contribute to a more favourable course of disease. This dissertation focuses on the improvement of current diagnostic methods that are applied for the recognition of bacterial and fungal pathogenic agents in patient samples such as blood and urine. The polymerase chain reaction (PCR) was used as a molecular technique for the detection and identification of clinically relevant bacteria and fungi out of various patient materials among which positive blood media. The implementation of such new tests enables a quick analysis (within one work day), as opposed to conventional medium-based methods.

Key words:

diagnosis infectious diseases, polymerase chain reaction  

“Propositional knowledge for conceptual understanding of statistics”

The applications of statistics in a daily and professional context are numerous, but there are even more examples of faulty applications of statistics in such a context.  Given the important role statistics play in research, politics, policy etc. it is of great importance that students and professional develop a good understanding of statistics. This requires a structured and phased approach. Characteristic for this approach is a fading degree of guidance by the teacher in consecutive phases, while the possibility of getting feedback on learning results continues to exist.

Key words:

statistics, application, learning

“Paternal impact on genetic integrity in newborns”

The quality of the DNA in sperm from potential fathers is under constant pressure because it is exposed to a great diversity of harmful substances. This can lead to transmission of DNA damage to the offspring with long-lasting health consequences. The research for this dissertation shows that a lifestyle with bad habits, such as smoking, has indeed a harmful effect on the DNA in the sperm. Even more important is that subsequently an indication was found for genetic effects of this damage in the offspring.

Key words:

DNA, sperm, health

“Strong Organisations in Weak States; Atypical Public Sector Performance in Dysfunctional Environments”

“Understanding regulation of gene transcription through epigenomics and cistromics. Unfolding ones and zeros into (un)folding chromatin”

Modern measuring technologies, such as microarray and sequencing technology, have resulted in an explosion of information in biomedical research. The big challenge for a bioinformatician is to develop computer procedures to distil biology from this bunch of ones and zeros. This dissertation crossed bioinformatics with epigenetics, the field that studies the form, not the content, of the genetic material we carry with us, and the influence this form has on the way the genetic material is expressed. The results have among others led to new methods of analysis and contributed to new therapeutic insights in the fight against cancer.

Key words:

bioinformatics, epigenetics, microarray, equencing technology

“Surgery in metastatic breast cancer”

At the time of the diagnosis, about 5% of breast cancer patients have metastases elsewhere in the body. This is called primary metastatic mammary carcinoma. Currently, the majority of these patients do not undergo breast surgery. In the last 10 years, several observational studies were published in which the removal of the breast tumour seemed associated with a survival advantage. This has been studied in more detail and confirmed in this dissertation. Moreover, this research studied the possible advantage of surgical treatment of the metastases in patients who develop these at a later stage, particularly of liver and lung metastases.

Key words:

Breast cancer, metastases, surgery

“De doorwerking van algemene rechtsbeginselen in de BTW (als uitgelegd door het Hof van Justitie EU)”

This research focuses on the application of general principles of justice (equality principle, proportionality principle, legal security principle) in the VAT jurisdiction of the EU High Court. It studies readings that have been developed in the jurisdiction and which the government has to follow. It also discusses the effect of the general principles of justice, such as ‘interpretation principle’, on the entire field of material tax law, in the way this has obtained a place in the VAT directive (who and what is taxed and on what, etc.) There also appears to be a connection between the general principles of justice and the legal disposition of the VAT.

Key words:

VAT, general principles of justice

“Kanker in context”

“Clinical and therapeutic aspects of Cerebral Palsy”

“Talking to Chromatin. Polycomb function in gene environment interactions”

A cell uses epigenetic regulation mechanisms to activate or deactivate genetic characteristics, i.e. genes.  Epigenetic regulators that belong to the Polycomb group protein complexes are important during normal development and physiological regulation, but they are also involved in the development of cancer. Not much is known yet about the exact way the Polycomb function is steered by the environment of a cell. This dissertation shows that the Polycomb function is dynamically regulated by environmental factors (such as growth factors, cell stress and oxygen), which in turn leads to a changed use of genes. These findings are very relevant for a better understanding of normal development and stem cell biology and also present leads for the development of selective therapies against cancer and applications in regenerative medicine.

Key words:

epigenetic regulators, Polycomb, genetic characteristics, environmental factors

“Magnetic Resonance Imaging for Evaluation of Gastric Motor Function”

“Ceramide transporters in neuroinflammation and neurodegenerative diseases”

“Treatment adherence in hypertension. Methodological aspects and new strategies”

“A ray of light. Evaluating the feasibility and effectiveness of routine psychosocial screening in cancer patients receiving radiotherapy”

About one out of three cancer patients experience psychosocial problems, such as feelings of anxiety and depression. The use of screening instruments can be useful for the identification of psychosocial problems. The research focused on the effects of using the Dutch Screening Inventory of Psychosocial Problems (SIPP) for the identification of psychosocial problems in cancer patients receiving radiotherapeutic treatment.  The research shows that using a screening tool in itself is not sufficient. By using the SIPP, the number of patients that were referred to psychosocial care providers had not increased and the communication between patient and radiotherapist had not improved.  However, the results show that patients are referred to a social worker at an earlier stage, which appears to have a favourable effect on some health related outcomes. Providing successful psychosocial care in the radiotherapeutic institutions is complex and requires a multidisciplinary approach.

Key words:

psychosocial screening, screening instrument, psychosocial care, cancer patients and radiotherapy

“Innoveren om beter te leren”

“Does Assessment Drive Students’ Learning? Clinical Context Assessment and Students’ Approaches to Learning”

The research aimes to understand how student react to summative or formative assessment within the clinical setup and to explore factors that direct the students towards deep learning approaches. This includes knowledge integration, writing summaries, self-testing, clinical problem solving and safe patient management. The conclusion is that several intrinsic and extrinsic assessment factors have been found to affect students' learning and learning approaches. Many of these factors were theoretically proposed but few of them have been already researched.

Key words:

learning, assessment, study strategies, clinical training

“Part-Time Employment and Human Capital Development”

This dissertation aims to analyze the connection between part-time employment and the development of human capital on three levels: employees, companies and children. Part-timers often appear to take less training because employers are less inclined to invest in them. This pattern mainly applies to lower educated employees and for them part-time employment therefore more often leads to lower hourly wages. On the other hand, companies in the services sector appear to benefit from part-time employment. The company productivity appears higher because the deployment of part-time staff is more efficient.  Also for the cognitive development of toddlers part-time work by mothers does not appear to have disadvantages.

Key words:

part-time employment, human capital

“Social Citizenschip Rights – Inequality and Exclusion”

This study looks at social citizenship rights, and examines the conditions that can explain inequality and social exclusion of newly entering groups of migrants/refugees into a host country’s society based on the variation in social policy towards these groups. The case of the Palestinian refugees in Jordan is examined and the impact of policies upon their entry is analysed. This study links the concepts of stratification, inequality, exclusion and citizenship and applies them beyond the western and industrialised societies, while still benefiting from the wealth of knowledge accumulated in studying these societies. With regards to the Palestinian refugees in Jordan the results indicate that those goups who didn’t receive nationality and those who lived in refugee camp housing fare consistently worse off than any other group in the society.

Key words:

social citizenship, inequality, social exclusion

“Patient and visitor violence in general hospitals”

Patient and visitor violence (PVV) in general hospitals is an underestimated problem. The dissertation investigates the occurrence and factors of this workplace hazard. Over half of the participating 2495 health professionals experienced PVV in the past year. Risk factors are connected to the personal characteristics of those involved, the interaction and the situation. Medical doctors experienced less violence than other health professionals. Young or inexperienced staff or staff working in emergency settings experienced more. Physical injuries occurred in 15% of the incidences.  Verbal violence was emotionally upsetting for almost all participants and most for who had experienced physical violence. In general the research results showed that strong institutional policies and procedures against patient and visitor violence are important in order to increase staff’s feeling of safety and in order to reduce the frequency of patient and visitor violence.  Focused training for specific staff groups, workplaces and interdisciplinary teamwork would also be beneficial.

Key words:

patient and visitor violence, general hospitals

“Treewidth; structural properties and algorithmic insights”

“Coping with mutant ubiquitin in health and neurodegenerative disease”

“Multimorbidity in general practice: Adverse health effects and innovative research strategies”

This dissertation shows that multimorbidity, i.e. having two or more diseases at the same time, is rather common in the general practice. Multimorbidity turns out to be related to negative health effects such as a permanent decline in physical health, memory complaints and cognitive functioning. The dissertation also shows that multimorbidity should not be confused with other old age constructs such as ‘frailty’ and ‘disability’; each construct has its own risk of admission to a nursing home and death. This dissertation also shows that innovative analysis methods can identify new and potentially relevant medical patterns in large quantities of medical data.

Key words:

multimorbidity, general practice, health effects

“Peri- and extravascular inflammation: impact on Atherosclerosis”

“On the Economic and Strategic Implications of Science”

“Assessment of genetic variation as a predictor of smoking cessation success”

Kleine aangeboren varianten in zogenaamde rokengerelateerde genen beïnvloeden de effectiviteit van het stoppen met roken behandelingen.

Small genetic variations in so-called smoking related genes influence the effectiveness of treatments for smoking cessation. This PhD research found several variations that influence the degree of addiction and chances of cessation after treatment with antidepressants. This knowledge can lead in the near future to a genetic test that can determine beforehand the most effective treatment for smoking cessation for individual smokers. Further research shows that smokers are aware of the importance of this type of test, particularly when it is offered by their general practitioner. General practitioners are also interested in offering it, but think they lack the time and the knowledge.

Key words:

smoking cessation treatments, genetic differences, genetic test

“Organizational Strategies, Firms’ Performance and Spatial Spillovers. The Canadian Case in Research and Development”

“Epicardial amiodarone therapy for atrial fibrillation”

Atrial fibrillation is a very common cardiac rhythm disorder that increases the risk of a stroke and early death. This PhD research investigated if the treatment of atrial fibrillation can be improved by delivering the drug amiodaron directly to the heart. The higher medicine concentrations in the heart and the lower concentrations in the rest of the body thus realize a greater effect while the risk of side-effects decreases. This dissertation describes various methods, such as injecting medicine solutions in the pericardium and applying (biodegradable) hydrogels and patches that can deliver medicines directly to the heart. The research shows that particularly this last method is effective in selectively suppressing atrial rhythm disorders while the medicine levels in the other parts of the heart and the body are limited to a minimum.

Key words:

atrial fibrillation, amiodaron, local application, hydrogel, patch

“De weg van nazorg naar voorzorg: Buiten de gebaande paden”

“The role of free fatty acids in ectopic lipid accumulation, insulin resistance and inflammation in humans”

“Bargaining and Judgment Aggregation”

“Computational analysis of β-adrenergic stimulation and its effects on cardiac ventricular electrophysiology”

Cardiovascular disorders often (~50% of the cases) manifest themselves suddenly in the form of ventricular arrhythmias leading to sudden cardiac death. The autonomic nervous system plays an important role in the induction of these arrhythmias, but the exact mechanisms contributing at the level of the individual cell remain incompletely understood. In this thesis, a systems-biology approach was used in which computer models were developed to investigate the effect of sympathetic stimulation (“stress”) on the electrophysiology of the cardiac ventricular myocyte. Using these models, the consequences of mutations in cardiac ion channels and/or pharmacological interventions were investigated and the ionic mechanisms were determined. Together with experimental research, this has provided novel insights into the cellular mechanisms contributing to “stress”-induced arrhythmias. These computational models provide a state-of-the-art framework to investigate cardiac electrophysiology and could in the future form the basis of novel approaches for personalized medicine by integrating available patient-specific information.

Key words:

arrhythmias, electrophysiology, computer models, systems-biology

“Staphylococcus aureus biofilm”

The pathogenic Staphylococcus aureus bacterium can, just as other bacteria, end up in the blood stream of patients with a wound or during the insertion of an intravenous catheter. In the blood stream the bacterium can attach to xenobiotic materials such as artificial valves or catheters. Bacteria can subsequently encapsulate in a matrix (biofilm) of self-produced mucus and blood components. The formed biofilm around the bacterium offers protection against the own immune system and against antibiotics. Bacteria in a biofilm are difficult to eliminate and they are responsible for regularly recurring infections.  This research studied the effect of rifampicin and other biotics against biofilm and investigated how biofilm formation can be prevented. A preventive strategy is to provide artificial materials with a coating that is both antimicrobial and antithrombogenic. It turned out that applying silver-heparin coatings is a promising approach.

Key words:

Staphylococcus aureus bacterium, biofilm, coating

“Skeletal muscle fatty acid handling in insulin resistance: the effect of dietary fatty acids”

The metabolic syndrome (MetS) is a cluster of risk factors (such as high blood pressure, a disturbed lipid balance, insulin resistance and obesity) for the development of type 2 diabetes (T2D) and cardiovascular diseases. Insulin resistance and central obesity are considered the main factors underlying MetS.  There is proof that the type of fat in food can change the insulin sensitivity of the muscle by influencing the storage and oxidation of fats in the muscle. This dissertation focuses on the fat metabolism of the skeletal muscle in relation to insulin sensitivity and it studies the effect of the quantity and the type of fat on that. The dissertation proves that changing the quality and quantity of food can lead to an improvement of the way the muscle handles fats and thus to an improvement of insulin sensitivity. However, the results also show that changes in the diet must be well adjusted to the genetic and metabolic profile of groups of people.

Key words:

metabool syndroom, vetopslag, skeletspier, insulinegevoeligheid

“Models in official statistics”

“Who cares? Studying various aspects of involving nurse specialists in primary care for urinary incontinence”

Involuntary urine loss is a common problem. The costs for incontinence requirements are high, annually 166 million Euros.  The number of patients increases as a result of the ageing population, and  consequently the costs increase. With adequate primary care, these costs could turn out considerably lower. This study shows that task support for GP’s from specialised urinary incontinence nurses would provide better quality of incontinence care at an acceptable price. Patients appeared very satisfied with the care by the nurses, who in turn were satisfied with their new tasks. The majority of GP’s found the role of the nurses useful. On the basis of these study results, the recommendation is to introduce this type of provision in primary health care, and to compare it with other, competing ways of incontinence care. This will provide more information in the future for the decision-making with regard to the concerned allowances for incontinence care.

Key words:

involuntary urine loss, treatment by FP, costs incontinence care

“European Contract Law between the Single Market and the Law Market”

“High-level visual object representations in inferior temporal cortex”

Visual object recognition is a computationally challenging task, but is accomplished by the human brain with relative ease. We used functional magnetic resonance imaging (fMRI) and a new method, representational similarity analysis, to investigate the brain mechanisms underlying the recognition of individual objects. We show that the representation of objects in high-level visual brain regions is inherently categorical and hierarchically organized, reflecting object categories of longstanding evolutionary relevance that match between human and monkey. Furthermore, perceived object similarity reflected the brain representation. Our work can be used to improve computational models of vision and offers a framework for quantitatively comparing brain and behaviour.

Key words:

object perception, brain, fMRI

“Genetic and nongenetic studies of schizophrenia”

“From vulnerability to resilience against depression. The value of daily-life positive emotions”

This thesis focuses on the role of emotions in resilience against depression. A series of daily-life studies suggests that especially positive emotions and enjoyment during pleasant daily-life situations are important in resilience against depression. The studies also showed that people can learn to experience more positive emotions in daily life. After a mindfulness training, people rated daily-life activities as more pleasant and experienced more positive emotions both overall and when engaging in pleasant activities. These increases in positivity went hand in hand with an improvement in depressive symptoms.

“Exploring the impact of diversity factors on problem-based collaborative learning”

“De doorwerking van natuurbeschermingsverdragen in de Europese en Nederlandse rechtsorde”

This dissertation investigates if the practice of the implementation of the nature protection treaties ratified by the Netherlands comes up to the doctrine on the implementation of treaties. The research shows that the implementation practice – particularly via the Judge – does not come up to this doctrine. On the other hand, the doctrine needs some more clarification, completion and actualization, and this dissertation provides and clearly describes these. The dissertation discusses eleven international treaties, among which the Bern Convention on the preservation of wild animals and plants and their natural environment in Europe; the Bonn Convention on the protection of migratory wild animal species; the Wetlands Convention and the Benelux Agreement of 1970 in the field of hunting and bird protection. As far as known, this is the first academic research that provides such an extensive analysis of all (living) area and species protection stipulations of each of the above mentioned treaties and compares these with the European en national nature protection legislation.

Key words:

nature protection treaties, doctrine, implementation 

“Predictive Toxicogenomics for the Identification of Chemical Carcinogens: Application to human hepatic cell lines”

For testing whether chemicals cause cancer to humans, numerous animals are used. Existing methods which do not use animals produce many false results. This thesis describes the development of a new method that successfully and more accurately identifies chemicals that cause cancer by damaging the genetic material of cells. This method does not use animals and therefore its application may reduce the use of experimental animals. For the development of this method toxicogenomics approaches – gene expression changes induced by chemicals – were applied to human liver cells, providing, therefore, more relevant results than animal testing. This thesis further shows that the application of such approaches to human liver cells helps us understand how chemicals affect normal cellular functions.

Key words:

chemicals, cancer, toxicogenomics, human cells 

“Focus on ad – Morphological alterations in mouse models of Alzheimer’s disease”

“Representation of the rewarding value of food in the human brain – Effects of dietary restraint, body weight, stress, and shifts in macronutrient intake”

“Snow white’s heritage: gender, social roles and alcohol use”

This thesis aimes to better understand and specify the conditions under which the relationship between social roles and alcohol use is most likely to be observed.According to the classic role theory: the higher the number of social roles the lower the drinking levels. The effect of roles is influenced by the extent to which social roles structure or fail to structure everyday life with meaningful activities. In general, family roles generally showed a higher protective impact on women’s alcohol use; among men a higher impact was found for socioeconomic factors. There is strong evidence for gender differences in how strongly social roles influence drinking. One of the central factors in explaining these gender differences is gender equity at the societal level: in societies with more gender equity, the additional role of maternal employment outside the home is more likely to decrease the mothers’ alcohol use.

Key words:

alcohol use, gender, culture, social roles

“Serving well by selling well”

“Prader-Willi Syndrome: genotype and phenotype at adult age”​

“Failure mechanisms of the lumbar disc prosthesis”

Lower back pains are a large social problem in today’s society. If conservative treatment (for example exercise therapy, pain medication) doesn’t help, a back operation can be considered. A relatively new technique is placing lumbar disc prosthesis to replace the intervertebral disc. It is not clear how these disc prostheses will turn out in the long term. In the MUMC+, 100 patients were seen with back and/or leg pain complaints after placement of a disc prosthesis. In a number of these patients, a repair operation was performed. Two repair operations have been compared. Both repair operations resulted in an improvement of the pain and the function. Moreover, large numbers of wear particles and inflammation cells turned out to be present in the tissue, comparable to reactions that occur in worn hip and knee prostheses.

Key words:

lower back pains, treatment, operation, disc prosthesis

“Rescuing A Patient in Deteriorating Situations (RAPIDS); A programmatic approach in developing and evaluating a simulation-based educational program”

“Molecular imaging of acute and healing myocardial infarction”

“Targeting PPARs in metabolic risk management: a pharmacological and nutritional approach”

“Exploiting geometric properties in combinatorial optimization”

A part of the thesis is devoted to a trajectory optimisation helicopter problem which originally came from Afghanistan and US army. Sometimes there is a need to evacuate soldiers from a battlefield to a hospital. A helicopter is normally used in this case. It has to avoid the mountains on the way; but because the air density is lower on high altitudes the helicopter loses its speed if it goes up. Therefore, it is not clear which trajectory is the fastest as it definitely does not match the shortest trajectory. We model this problem in several ways and obtain the theoretical fastest trajectories without obstacles. These results are also used to design an effective algorithm for one of the obstacle cases. Further research may lead, for example, to a quick helicopter route planner which minimizes the time of a trip.

Key words:

trajectory optimization, helicopter, algorithm, routepanner

“Blood-contacting biomaterials for critical clinical applications”

“Non-invasive measurements in wheezing preschool children”

About 30% of preschool children suffer from asthmatic complaints, such as wheezing. Only 30% of these children develop asthma, the rest loses the complaints as they grow older.  Wheeze is a complex complaint and it is not known whether, as in asthma, it is accompanied by bronchial infection. This dissertation shows that wheezing children exhale more inflammatory substances than children without complaints. This indicates an increased bronchial infection. Inflammatory substances in the exhaled air were determined by means of a patented instrument. Measuring inflammatory substances in the exhaled air is an innovative and non-invasive way of early detecting bronchial infection. This enables a quicker en more effective treatment of this very common bronchial complaint.

Key words:

wheeze, asthma, bronchial infection, breath, children

“Microvascular actions of insulin: studies on the interaction with angiotensin II and on the postprandial state”

“Mijnbouw en Arbeidsmarkt in Nederlands-Limburg”

This dissertation studies the policy of the mining management for recruitment, selection and binding of the personnel to the company, as well as the consequences of this policy for the composition of the miner’s population. Miners’ sons from the own region, other Limburg inhabitants, other Dutchmen, and only then foreigners, that was in general the order that was followed in recruiting personnel.  In the case of compulsory redundancies, the order was the other way around. That is how the Limburg mining managers ultimately succeeded in their objective to build a workforce from mainly ‘own people’. That result was achieved through very conscious recruitment and binding strategies, but also thanks to favourable circumstances.

Key words:

Limburg mining industry, personnel policy

“Decision making in surgical treatment of chronic low back pain”

Chronic low back pain is the most common cause of absenteeism in our society. When painkillers and exercise therapy don’t give results, a painful vertebra can be surgically fastened. This so-called spondylodesis operation indeed adequately lowers the pain for certain patients, but the results vary strongly. Spine specialists use prognostic tests to predict the result. For this dissertation Dutch spine experts were interviewed about their selection criteria for spondylodesis in daily practice. This showed a considerable difference between physicians in the use of prognostic tests and the treatment of chronic low back pain. After analysis of a large patient cohort and a subsequent systematic literature study, it turned out that none of the tests has sufficient predictive quality for use in the daily medical practice. The results of spondylodesis in chronic low back pain remain unpredictable, with consequences for patients, health care Insurance companies and policymakers.

Key words:

Chronic low back pain, spondylodesis, prognostic tests, patient selection

“Bargaining power in strategic games and economic decision-making”

“Op weg naar zichtbaarheid”

“Le Droit Maritime International et le transport des Hydrocarbures”

Preventive and curative fight against oil spills are an undeniable fact nowadays. The law system of prevention of oil spills regulates the construction of ships and emissions of hydrocarbons. It estab-lishes, inter alia, double hull and on shore reception facilities requirements. Curative measures con-sist in operational measures and compensation rules for victims of oil spills. However, fight against oil spills in Africa is thwarted by the lack of integrated emergency response plans. Compensation rules are sufficiently underdeterrent in comparison with classic rules of evidence of oil pollution damages and the causal link between these damages and the polluter ship activity. 

“Spinal cord stimulation in neuropathic pain, technical aspects and effectiveness”

“On the alignment of the European Patent Convention and the Patent Cooperation Treaty with requirements of the Patent Law Treaty”

In 2000, a new international patent treaty (Patent Law Treaty) was established, which ‘streamlines and harmonizes’ the formal requirements that patent granting bodies can impose with the submission of patent applications.  The intention is that existing patent laws are adjusted to this. However, because very many conditions are not compulsory, the new treaty leaves to much freedom in their implementation in the existing patent laws. Consequently, not much streamlining or harmonizing was realized. To keep the new patent treaty as simple as possible, one often refers to another international patent treaty (Patent Cooperation Treaty); because of that, these two treaties are legally linked. It is therefore very peculiar that particularly this patent treaty has not been aligned with the new treaty. 

“Dual allegiance in organizational teams”

The function of a management team is to coordinate the organizational tasks from different perspectives with managers from various disciplines.  In doing so, each manager comes across sub-interests that depend on the position (for example region or division manager), or the function he/she represents (for example HR, sales, finance). For successful functioning of a management team the mutual relations are important. For the improvement of team functioning, usually the influence of personality traits is studied. This dissertation, on the contrary, analyses how the representation of sub-interests influences the team functioning. This research shows that when these sub-interests are not taken into account with the decision-making, managers can experience an internal conflict between the various sub-interests. This obstructs a good mutual relation and consequently the team functioning.

Key words:

management team, functioning

“Nucleo-cytoskeletal interactions in the mechanical functioning of the cell”

The central question in this dissertation is what happens when the mechanical network that supports the cell nucleus is disturbed.  The role of lamin proteins is crucial here. They form the lamina that gives the cell nucleus the necessary firmness and connects it to the cell skeleton. When lamin A/C is disturbed, the cell nucleus weakens: cracks develop in the nucleus membrane and the nucleus itself becomes weaker and less resistant to mechanical forces. Also in the surrounding cell skeleton all kinds of deviations develop, which affect the normal functioning of the cell. This leads to a range of diseases that are together called ‘laminopathies’.

Key words:

celkern, lamine-eiwitten

“Molecular progression markers in cervical premalignancies. Development of a diagnostic MLPA-assay”

All over the world, cervical cancer is a very common type of tumour. Infection with the Human Papilloma Virus (HPV) is the main risk factor, but the virus can only cause cancer in combination with other factors. This research investigated if it is possible to identify malignant cervical deviations by searching for other risk factors than the infection with the carcinogenic HPV alone. For this purpose a test was developed that can detect a series of these risk factors, such as the number of virus particles and incorporation of the virus in the human DNA. Also deviations in certain human genes could be shown in these tumours. With this newly developed HPV MLPA test, we are capable of identifying malignant cervical deviations with 85% accuracy.

Key words:

cervical cancer, HPV, MLPA

“A disrupted balance? Prevention of terrorism and compliance with fundamental legal rights and principles of law – the Dutch anti-terrorism legislation”

Since 9/11, combating terrorism has gained top priority in Dutch politics. The counter terrorism policy  primarily focuses on prevention and has led to extensive anti-terrorism legislation. This thesis discusses the scope of the Dutch anti-terrorism legislation within and beyond criminal law and its impact on principles of (criminal) law and fundamental legal rights. To what extent are the statutory criteria for the application of pre-trial anti-terrorism powers and measures, and their practical implementation, in compliance with the relevant fundamental legal rights and principles of law as enshrined in European treaties? Firstly, it is ascertained what constitutes an act of terrorism according to the Dutch criminal law system, and how the criminalisation of terrorism affects criminal liability. Secondly, the thesis discusses what level of suspicion is required to apply which powers and/or measures to counter terrorism. Thirdly, the way the application of these state powers affects which fundamental legal rights and principles of law is scrutinised.

Key words:

criminal law, anti-terrorism legislation, fundamental  rights

“Reconciling Privatization with Human Rights”

Under the influence of globalisation many countries have been compelled to privatise the provision of a number of State and public services. This trend towards privatisation has been met with skepticism from the human rights world. In this study, the privatisation phenomenon is analysed with the aim of establishing whether it can be reconciled with the human rights obligations of States. 
The study addresses the issue of accountability for the conduct of entities exercising governmental functions and discusses the need for a new model where privatized entities are directly accountable for human rights abuses. It also focuses on two case studies involving privatisation in two different sectors: the alleged abuses of contractors from two private military and security companies in Abu Ghraib, Iraq, and the privatisation of water in the city of Buenos Aires, Argentina.

Key words:

globalization, privatization, human rights, regulation

“Caring about Care; investigating the effects of different Communication styles in medical and educational credence Services”

Within this PhD research the focus was on services that customers might not be able to judge due to lack of knowledge. The studies investigate how the communication style of service providers – here physician and teacher –  might influence attitudes (e.g. satisfaction) and behaviors (e.g. compliance or helping behavior) of customers – here patient and student. We differentiated between two types of communication styles: care communication (also known as socio-emotional) and cure communication (task-oriented). We found out that different communication styles trigger different feelings which ultimately influence desired outcomes. Furthermore, we could demonstrate that certain communication style is especially beneficial for certain personality traits in order to perform a desired behavior (e.g. care communication could help shy students to exhibit helping behavior within the classroom).

Key words:

communication styles, emotions, credence services, satisfaction, compliance, helping behavior

“Legitimacy of Humanitarian Military Intervention”

Moral and legal justification of the ‘humanitarian military intervention’ (HMI) concept and its applications are highly problematic undertakings. This study proposes a radical departure from the difficult normative debates by empirically assessing the degree of ‘humanitarianism’ behind 1114 cases of military interventions in the period of 1946-2005. The novelty of this approach is based on a systematic evaluation of the ‘humanitarianism’ behind the ‘motives and means’ of individual military interventions on the one hand, and of the ‘humanitarianism’ behind their ‘outcomes’ on the other hand. The findings of the study map the general trends and associations among the factors, indicating that it is really possible to achieve ‘humanitarian ends’ using ‘military means’, but only under limited circumstances.

Key words:

humanitarian military intervention, justification

“Patient enablement: a living dialogue. Exploring perspectives on patient enablement and consultation quality”

“Nutritional and genetic determinants of cognitive ageing; A neuroepidemiological approach”

“Cross cultural studies on adolescent cannabis use and psychosis”

This dissertation presents epidemiological studies into the effects of cannabis use during adolescence. The results show that the use of cannabis increases the risk of psychotic symptoms. It turns out that the earlier the adolescents start using cannabis, the bigger the risk of becoming psychotic later. This effect appeared to have disappeared when they used cannabis after their 14th year of age. This the first time this connection is also shown in non-Western societies. Furthermore, two Dutch and Greek studies are described, showing that adolescents, who experienced traumatic events in their childhood, are more sensitive to the psychotic effects of cannabis.

“Staff Development in Higher Education Working to improve practices of experts in educational development of teachers and transfer of learning to the workplace”

“Dynamic Microsimulation for Public Policy Analysis”

This dissertation studies an increasingly important policy modelling tool: dynamic microsimulation. Dynamic microsimulation can be used to forecast lifetime social economic profiles of every individual in a society and analyse how these interact with public policies. The research shows that, with the help of a microsimulation model, it is possible to reconstruct an individual career path using limited available data. In addition, this dissertation improves the accuracies in simulating individual employment options and the timing of retirement. The study also analyses how microsimulation results are affected when combined with certain macro projections. These methodological improvements in microsimulation may help researchers and policymakers to explore intended and unintended effects of public policies with greater details and accuracies, even before these policies are implemented.

Key words:

microsimulation, individual profiles, public policy, individual career path

“Effects of Air Pollution on Haemostasis and Atherosclerosis”

Air pollution is a part of urban life and consists of small particles (particulate matter; PM) in different sizes and gases. The associations of PM with cardiovascular health including thrombosis and atherosclerosis have been suggested but the underlying mechanism is not fully understood. A thrombus is formed upon an imbalance in the blood coagulation system. In this dissertation, the procoagulant effects of PM and gases are reported based on extensive experimental studies. The focus of the research was on the two main pathways of blood coagulation; the tissue factor dependent and especially the factor XII dependent pathway. From the cardiovascular perspective, the effects of biodiesel exhaust as an alternative fuel to conventional diesel in the progression of atherosclerosis, are compared.  The name biodiesel is misleading, given its harmful vascular effects as compared to regular petroleum diesel.

Key words:

air pollution, particulate matter (PM), biodiesel, cardiovascular diseases, blood coagulation

“Semi-Nonparametric Indirect Inference”

“Informal payments for Health Care Services in Albania”

“The role of rumination in the development of depressive symptoms in youth”

Can adolescents become depressed from negative thinking? This dissertation addressed the question to which extent continuous worrying about depressive feelings and stressful events (ruminating) is connected to depressive complaints in adolescents. Studies show that ruminating is strongly connected to depressive complaints, already from the age of ten. However, the effect of ruminating on later depressive complaints is modest. This summons the question to which extent ruminating is a risk factor for the development of depression or a side-effect. Future research will have to focus on the causality between ruminating and depression in adolescents.

“Mechanisms of surface perception uncovered by visual illusions”

“Endometrial maturation: the role of oestradiol and progesterone”
 

“Incentives in the diagnosis treatment combination payment system for specialist medical care”

This dissertation studies several new financial incentives for doctors and hospitals since in 2005 the Diagnosis Treatment Combination (DBC) system was introduced. It turns out, among others, that the production in that part of the hospital care where payment takes place per operation (the so-called B-segment) has increased and that a more expensive DBC is chosen than medically necessary (upcoding). Empirical proof was found for all these effects. Exactly how big this total effect is cannot be quantified, because it is not possible to extrapolate for all analyses to the entire sector of specialist medical care. 
Parts of the current DBC problems will be solved with the introduction of DOT in 2012, but the risk of upcoding will continue to exist. Monitoring and benchmarking institutions both with regard to case mix as volume by health care Insurance companies will be the main challenge for 2012.

Key words:

DBC system, medical specialists, hospital

“Droit International de l’environnement et mise en oeuvre du droit a l’eau potable en Afrique centrale: le cas du Cameroun”

For years, numerous studies and conferences were focused on the right to water, but, none of them have solved the problem of guaranteeing it. Several texts recognized the existence of this right, without giving it the character of binding law. This thesis seeks to: give to the right to drinking water a better definition, find against whom this right must be guaranteed, transpose the best situations in Central Africa and in Cameroon in particular, find sketches solutions to difficulties encountered in implementing this right in Cameroun.

Key words:

international environmental Law, right to drinking water, Central Africa, Cameroun

“Bee-inspired Distributed Optimization”

Despite the fact that the honey bee has a limited intelligence, she is capable of amazing achievements. By cooperating and distributing tasks so-called swarm intelligence is created. That way, they can solve amazingly complex problems, such as effectively searching food in an unknown world. Many of these problems are similar to problems we people try to solve, the so-called combinatory optimization problems. An example is navigation software: find the shortest/fastest/cheapest route. For this PhD research the behaviour of the honey bee and the resulting swarm intelligence is a source of inspiration for making optimization algorithms with artificial swarm intelligence. The results of this research show that bee-inspired swarm intelligence is promising/performs well in solving combinatory optimization problems.

Key words:

Swarm intelligence, combinatory optimization problems, honey bee

“De menselijke motor”

“Surgical Treatment of Secondary Hepatic Malignancies’

“Fatty acid metabolism in the metabolic syndrome”

The metabolic syndrome is a combination of risk factors for diabetes 2 and cardiovascular diseases. Both an increased fat level in the blood as disorders in the muscle fat metabolism can lead to undesired fat accumulation in the muscle tissue, which can disturb the working of the hormone insulin. This dissertation shows that replacing saturated fats in food by complex carbohydrates and a fish oil supplement lowers the risk of metabolic syndrome, particularly through effects on the fat level in the blood. The replacement of saturated fats with unsaturated fats or complex carbohydrates has little influence on the muscle fat metabolism and the working of insulin in persons with metabolic syndrome.

Key words:

metabolic syndrome, fat metabolism, food

“Physical functioning in low back pain”

“Gezondheidsbevordering en voortgezet onderwijs, verstandshuwelijk of echte liefde?”

This research shows that health holds no structural position in the policy and practice of schools for secondary education. Schools recognize the need of attention for the students and their physical and social environment, but due to many obligations imposed by the authorities they are forced to make choices. Still, this dissertation offers leads for improvement: 

• Better connection to educational goals.
• Support based on the wishes and needs of schools. 
• Bearing in mind the possibilities in a school and the results the school has to show.
• Offering intensive guidance in the change process of schools with the introduction of a new policy.   

Key words:

school health policy, secondary education, options for improvement 

“Social Integration of people with intellectual disabilities in neighbourhoods: Sitting on the fence”

In the Netherlands, people with intellectual disabilities (ID) are increasingly living in small scale care facilities in regular neighbourhoods. This thesis discusses the concerns about social integration of people with ID. From the opposition often expressed by (potential) neighbours about accepting people with ID in their neighbourhood, to the lack of interest in social contact with neighbours with ID after they have moved in. The underlying mechanisms responsible for the different social responses to anticipated contact with neighbours with ID, and the daily reality of interactions between neighbours with and without ID are illustrated. This knowledge can help improve neighbourhood social integration of people with ID.

Key words:

intellectual disability, social integration, community care, attitudes, intergroup contact

“Uitgebalanceerd”

“Supporting healthcare professionals to encourage patients to decrease cardiovascular risk attributable to physical inactivity”

People with one or more cardiovascular risk factors and an inactive lifestyle have an increased risk of cardiovascular diseases and diabetes type 2. This dissertation studies the effectiveness of the ways in which health care professionals incite these people to exercise. The fact is that by improving the cardiovascular condition, the risk can be reduced. Intensive physical activity turns out to have the biggest risk reducing effect. People who become ‘physically fit’ as a result of intensive exercise, reach the best results. Shortly, it is not so much ‘that’ you exercise, but ‘how intensively’ you exercise.

Key words:

cardiovascular risk factors, physical fitness, exercise

“Multifocal Intraocular Lenses in Cataract Surgery”

“The dissemination of the healthy diet program; Krachtvoer for Dutch prevocational schools”

For quite some time already, the task of schools is no longer limited to knowledge transfer.  Krachtvoer is a healthy diet programme on breakfast, fruit and snacks for the first and second grades of prevocational schools. The aim is to get students to think about their own eating habits and, if necessary, to try and improve them.  The programme often uses practical methods, such as test lessons or a recipe competition. Schools are supported by the municipal health services (GGD) for the implementation of Krachtvoer.  This dissertation presents a scientific evaluation of Krachtvoer and the support by the GGD with the programme. The classes are well appreciated by students and teachers and they lead to an improvement of the fruit and snack habits of students.

Key words:

Krachtvoer, eating habits, prevocational students

“Learning to diagnose using patient video cases in paediatrics: perceptive and cognitive processes”​

“De idylle voorbij; verbeelding van moederschap in Nederlandse literatuur 1980 tot 2010”

Motherhood is nowadays imperatively idealized in Dutch society. Consequently, many mothers don’t experience it as natural to speak about the unpleasant sides and experiences of motherhood.  Contemporary Dutch literature, however, particularly describes mothers who don’t (can’t) fulfil this ideal. They lose control and get off the right track. The dissertation focuses on the relation between this type of novels and the social motherhood ideal, bringing together literature sociological research and novel interpretations in an innovative way. The analysis of four novels by Vonne van der Meer, Saskia Noort, Renate Dorrestein and Maya Rasker is at the centre of the dissertation. One of the conclusions is that literature can retort the conventional rosy motherhood ideal. 

Key words:

motherhood, unpleasant sides, literature  

“Microarray-based expression signatures: potential application for individualized cancer treatment”

Identifying new biomarkers and setting therapeutic targets to improve treatment is one of the spearhead aims of cancer research. It is clear that more precise methods for the prediction of treatment result and determination of optimal treatment per individual are necessary. The use of new techniques such as gene expression micro arrays (or gene chip) offers the possibility to identify new markers, but the analysis of this type of data is not uncomplicated. By means of this technique a biomarker was developed that can be used for several cancer types. Moreover, methods were developed to improve the quality of gene expression based markers, which will lead to quicker use in the clinic. 

Key words:

biomarker, cancer, gene expression micro arrays

“BTW-verleden met perspectief”

“Pulsing response of the cardiac transcriptome”

“Rural Nonfarm Employment and International Migration as Alternatives to Agricultural Employment; the case of Kyrgyzstan”

“When all eyes are on you; studies into threat processing and pharmacological treatment of social anxiety disorder”

Social anxiety disorder is a disabling psychiatric disorder characterised by an extreme fear of negative judgement by others. The disorder is often accompanied by other disorders, such as depression and alcoholism.  This thesis demonstrates that persons with a social anxiety disorder show dysfunctional processing of threatening information (such as angry faces).  Furthermore, persons with social anxiety thoughts turn out to be at a higher risk of developing paranoid thoughts later on, possibly especially when they use cannabis. Therefore, social anxiety as extra risk factor for paranoia should be added to the information that is used in the current psycho-educational programmes on drug use and psychiatric symptoms in Young people. Moreover, the thesis shows that medication treatment of the social anxiety disorder is far from satisfactory.

Key words:

Social anxiety disorder, information processing, medication, information

‘Climbing the Pyramid; towards understanding performance assessment’

The studies presented in the thesis show that hemolysis (the spread of red blood damage) plays an important role in the development of organ injury during cardiovascular surgery. The focus lays on disturbances in microcirculatory perfusion and induction of injury to the gut and kidneys during acute hemolysis. Therapeutic options, mainly the inhalation of nitric-oxide gas, to counteract the deleterious effects of hemolysis on microcirculatory blood flow and the development of organ injury are studied and discussed.

Key words:

hemolysis, cardiovascular surgery, organ injury

“Exploring the Influence of Contextual Factors of the Clinical Encounter on Clinical Reasoning Success”

Context specificity refers to the phenomenon that physician’s clinical reasoning performance (decision making) can vary from patient to patient. This thesis sought to unravel this phenomenon through exploring the influence of context on clinical reasoning performance. 
First, we define context and outline contemporary theory to explore this phenomenon.  Next, we found that selected contextual factors (patient, physician, practice) do influence experts’ clinical reasoning performance and we identify several potential mechanisms.  We then explored medical students’ clinical reasoning and found that the authenticity of instructional format did not significantly impact subsequent clinical reasoning performance. Finally, we explored functional neuroimaging correlates of clinical reasoning expertise and found evidence to support contemporary theory.  

Key words:

Clinical reasoning, context

“MRI of the therapeutic neovascularization: morphology & function”

For patients with leg and coronary artery stenosis treatments such as dotter and bypass operations are not always effective. Currently, research is conducted into stimulating the growth of new blood vessels that can repair the tissue blood circulation in these patients. To evaluate and steer the effectiveness of these therapies at an early stage non-invasive techniques are necessary. This dissertation describes MRI techniques that can image the new blood vessels and their influence on the tissue blood circulation. It also discusses solutions for the challenges that imaging the vessel growth involves. This is an important step in the evaluation of vessel growth therapy. 
This research was financed by the Nederlandse Hartstichting. 

Key words:

neovascularization, MRI, peripheral and coronary arterial disease

“Glaucoom. Druk, druk, druk…”

“Interactions in Psychosis; linking environment, brain and genes”

The mechanism behind the link between stress and psychosis is still not sufficiently known. This dissertation studies among others biological and genetic markers of stress sensitivity. In a subgroup of people with a psychotic disorder, increased stress sensitivity appears to be associated with a smaller hippocampus (a brain area that is involved in the storage of new memories) and with the ‘Met/Met genotype’ of the COMT gene. In people with increased psychosis vulnerability also a raised cortisol reaction to stress appears to be connected with subclinical psychotic experiences (subtle psychotic experiences, such as suspicion, which everyone has at times). 

Key words:

psychosis, stress, biologic markers

“Multi-modality imaging for treatment response evaluation in rectal cancer”

This dissertation studies the use of medical imaging, particularly Positron Emission Tomography (PET), for the evaluation of the treatment response in rectal cancer. Changes in various processes within the tumour were correlated with each other, but the correlation with pathological tumour regression was also studied.  
The results show that a precise prediction of the treatment response of the tumour is already possible at an early stage (two weeks after the start of the treatment) on the basis of PET imaging. The results also show that the delineation of the tumour (drawing of the tumour, distinguishing the tumour and the surrounding healthy tissue) does not necessarily have to be done manually by the radiotherapist-oncologist, because automatic and very precise tumour delineation is possible on the basis of PET imaging. The results presented in this dissertation are the first step towards patient specific treatment plans.

Key words:

rectal cancer, PET, treatment

“Essays in Matching with Money and Networks”

For a model in which any two agents can trade via bilateral contracts, assuming that their preferences satisfy some natural assumptions, we show that stable solutions can always be guaranteed to exist. Algorithms for finding one such stable solution are available. Applications may be possible in matching markets for couples and electricity markets.
Discussing the most prominent methods used for evaluating scientific output we show that they do not distinguish quality from quantity at article level. The systematic bias we find is analytically tractable and implies that the methods are manipulable. We introduce modified methods that correct for this bias.
The PhD was financed by NWO under grant VIDI-452-06-013

Key words:

bilateral contracts, algorithms, evaluation methods

“The road to adolescent traffic safety is paved with good intentions: Towards a theory- and evidence-based approach in traffic safety education”

“Poverty alleviation: Aid and social pensions”

“Heraclitische ethiek. Omgaan met de soft impacts van technologie.”

“Bestuurlijk gedonder”

In local administration in the Netherlands, mayors, aldermen or entire city councils are increasingly often forced to resign. In some communities this occurs so often that these communities have become known for the large amount of administrative problems that occur or have occurred.  This dissertation studies how many of these ‘administrative problem communities’ there are in the Netherlands, measured over the period 1998-2010, and what is the cause of the continuous problems. From a list of nine communities, four were investigated. The main conclusion is that in administrative problem communities a number of problem causing factors are assembled, while inhibitory factors (sometimes temporarily) are lacking.  Met name het ontbreken van goede communicatie in de coalitie jaagt problemen aan, terwijl de burgemeester juist remmend kan werken.

Key words:

administrative problem communities, causes

“Insulin resistance and mitochondrial function; a mitocentric view”

Results in this thesis show that patients with type 2 diabetes, as well as first-degree realatives of type 2 diabetic patients, have a lower capacity to burn fat and sugar. Mitochondria are the organelles where the burning of fat and sugar finds place. These mitochondria have a lower functionality in muscle of type 2 diabetic patients, which could lead to fat accumulation in the muscle and insulin resistance. These mitochondrial defects, however, restore upon a 12-week physical exercise-training programme. We also found that endurance trained men are better protected against the negative effects of fat on insulin sensitivity. We conclude that physical exercise is capable to restore compromised mitochondrial function in type 2 diabetes and that it has a protective role against fat accumulation and the development of insulin resistance. Mitochondrial function and insulin sensitivity are, however, not per se causally related, and are two independent mechanisms involved in the development of type 2 diabetes.

Key words:

type 2 diabetes, physical activity, mitochondria

“The role of arginine in human healing”

Accelerating wound healing is very important for patients with for example burns of chronic wounds. This dissertation studies the role of the amino acid arginine in this healing. Animal experiments show that arginine considerably accelerates wound healing in animals. The hypothesis was that human skin and wounds use arginine. The first part of the hypothesis was confirmed. Moreover, the results suggested that during normal human wound healing arginine is used. However, a study into the effect of arginine addition on wound healing (of surgical wounds) showed no positive effect.
This research was conducted with financial support from the Dutch Burns Foundation and the ‘Profileringsfonds’ of Maastricht University Medical Center.  

Key words:

wound healing, arginine

“Fysiologie als metafoor”

‘Venous cryo surgery of the leg’

The surgical treatment of varicose veins is one of the most performed interventions worldwide. Because of the enormous amount of operations this also involves considerable costs. Each improvement of technique can lower the risks of relapse and the costs and increase the quality of life. Historically, the surgeon ‘stripped’ the varicose vein from the leg by means of an operation. In the last ten years, the treatment has become increasingly less invasive and has for example been replaced by the laser treatment. An alternative treatment of the classic strip operation is the cryo strip surgery in which the vein is frozen out of the leg. 
This dissertation shows that this cryo strip is less effective than the classic strip surgery and should in fact no longer be used. It also turns out that the modern treatment of varicose veins by means of laser or other sources of heat is not better than the old strip surgery (that is even less expensive).  

Key words:

varicose veins, strip surgery, cryo strip, laser therapy

“The Metabolic Syndrome and Cardiovascular Disease: The CODAM study”

‘Surgical management of chronic inguinal pain syndromes’

“Interrupted Innovation; Emerging economies in the structure of the global aerospace industry”.

Key words:

aerospace manufacturing; latecomer industrialization; technological capabilities; sectoral systems of innovation

“Connecting the dots; functional networks and cognition in chronic epilepsy”

Aircraft and spacecraft manufacturing has been a privileged sector of leading industrialized economies because of its high technology and capital intensity. Statistical data on aerospace manufacturing compiled for the first time for nearly 50 countries and 50 years shows that only a few of the latecomers have succeeded in creating sustained growth in the sector. The study shows that competitive pressures and the cyclical nature of the industry require the establishment and periodical restructuring of sectoral innovation systems. The evolution of aerospace innovation systems are discussed in greater detail in the cases of Brazil, China, Argentina, Indonesia and Singapore.

“Hemolysis, microcirculatory changes and organ injury induced by cardiovascular surgery”

The studies presented in the thesis show that hemolysis (the spread of red blood damage) plays an important role in the development of organ injury during cardiovascular surgery. The focus lays on disturbances in microcirculatory perfusion and induction of injury to the gut and kidneys during acute hemolysis. Therapeutic options, mainly the inhalation of nitric-oxide gas, to counteract the deleterious effects of hemolysis on microcirculatory blood flow and the development of organ injury are studied and discussed.

Key words:

hemolysis, cardiovascular surgery, organ injury

“New developments in Sacral Neuromodulation for Lower Urinary Tract Dysfunction”

Function disorders of the bladder are a serious health problem. Globally it concerns patients with an overactive bladder (often combined with urine loss) and patients with a dysfunctional bladder evacuation. In the first instance treatment consists of pelvic floor therapy and medication. However, a large part of the patients insufficiently benefits from this or cannot stand the side-effects. Sacral neuromodulation is a relatively new treatment. The nerves of the bladder are stimulated with a subcutaneous stimulator, which helps the patients gain control over their bladder again. This dissertation shows that this treatment is safe and long term effective. After approximately 5 years the treatment is successful in 64 % of the patients.  

Key words:

bladder, function disorders, sacral neuromodulation