Academic Ceremonies October 2012

“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