“Interaction mechanisms of platelets and coagulation”

“Non-Alcoholic Steatohepatitis: Second Hit or Strike Out?”​

“Resisting temptation: The effect of an impulsive personality and a toxic environment on overeating”​

“Endometrial wave-like activity in assisted reproduction”​

“PPARs as  Modulators of cardiac remodelling”

“Postoperative autologous retransfusion of shed blood in primary total hip and knee arthroplasty”

“Oral Health Promotion and Tobacco Control in South Africa”

“Heterogeneity in human Aherosclerotic gene expression profiles : from man to macrophages”

“Bioinformatics and molecular biology”

“Regulation of cardiac long-chain fatty acid and glucose utilization: studies with cardiomyocytes from genetically manipulated mice”

“Neurovision, neuroimaging studies of illusory perception”​

“Regional Sustainability-tools for integrated governance”​

“Risk Aversion and Equilibria, Intertemporal Transfers, Strategic Claims”

“Optimization of  radiotherapy in Lung cancer treatment: balance between survival and quality of life”

“Measuring the performance of geosimulation models by map comparison”

“Dietary parp-1 inhibitors as anti-inflammatory compounds”

“Over de streep-grensarbeid vanuit Zuid-Limburg naar Duitsland, 1958-2001”

“Herstelrecht en procedurele waarborgen”

“Optical Biopsy in the Anterior Segment of the eye”

“Prevalence and Predictors of Acute and Chronic Pain after Surgery; the out-patient part of the story”

“Prevalence and Predictors of Acute and Chronic Pain after Surgery, the inpatient part of the story”

“Nutritional Modulation of DNA Repair”

“The role of B-glucan, plant stanols, and oxy(phyto)sterols in managing cardiovascular risk”​

“Urinary incontinence in primary care diagnosis and interventions”

“Correlation between irradiation and maxillary/mandibular bone vascularity, bone mineral density as well as implant stability”

“Free movement of lawers in the European Union”

“Gewekt vertrouwen in Europees perspectief”​

“Learning in Internships, What and how students learn from experience”

“Pre- and peri-operative assessment of the adnexal mass”​

“Europeanisation of Administrative Justice? The influence of the ECJ’s Case Law in Italy, Germany and England”​

“Determinants of ecstasy use and harm reduction strategies”

“De Maastrichtse School”

“Malaria and  Anaemie. The impact on maternal and perinatal outcomes.”

“Due diligence . Een beschouwing over het due diligence onderzoek volgens het Nederlands recht”

The book contains a comprehensive study of the phenomenon of due diligence ("suitable caution" or "due attentiveness"). A due diligence investigation is conducted when business transactions are concluded, such as mergers and take-overs and capital market transactions. "From the outside" it is not possible to see if liabilities are taken aboard (hidden financial obligations). A due diligence investigation is carried out to avoid disappointments afterwards. This dissertation describes everything that is involved with due diligence. One of the main conclusions is that in case of a transaction both parties have an investigation as well as a notification obligation. 

“Articular cartilage lesions; Advances in conservative and surgical  interventions”

A cartilage lesion in the joint does not recover spontaneously, and ultimately it will lead to complaints and wear. The initial treatment is conservative and can consist of administering hyaluronic acid in the joint. This dissertation shows that hyaluronic acid has a preventive effect on the surrounding cartilage. When conservative treatment fails, surgical intervention is an option. One of the new cartilage repair techniques is the so-called scaffold tissue-engineering; the implantation of a porous carrier material, without or with cells, in the cartilage lesion. The recovery after implantation of various carrier materials was compared and the risk of inflammation was determined. 
Collection box foundation that sponsored part of the printing costs: the Anna Foundation SenterNovem financed the experiments. 

Key words:

cartilage, tissue-engineering

“Natural Ah receptor agonists in the human diet : beneficial food components or unperceived risk factors?”

Dioxins activate the Ah receptor signal protein and this causes the toxicity of these environmental polluters. Some natural substances in vegetables and fruit also activate this Ah receptor. Studied was for this dissertation if these natural Ah receptor agonists (NAhRA"s) can have effects that are comparable to the dioxins" effect. In cultivated intestinal cells the influence is similar on an important step in the production of proteins (gene expression). Besides that, NAhRA"s can have positive as well as negative effects on DNA damage. After eating products with many NAhRA"s, Ah receptor activation effects appear not clearly demonstrable. A probable reason may be that NAhRA"s are quickly broken down and dioxins are not. However, frequent consumption of high doses of NahRA"s via food supplement is possibly not without risk. 

Key words:

natural Ah receptor agonists (NAhRA"s); DNA damage; food supplements

“Psychophysiology and the detection of deception: Promises and perils”

The use of the traditional lie detector is controversial. It has no solid academic foundation and the margin of error is considerable. Yet, registering physical reactions can be useful in police tracing. Not as a lie, but as a memory detector. That can be done by means of measuring the brain activity, but also on the basis of reactions of the autonomous nerve system, such as the transpiration in the hand palms. That way, for example the presence of offender knowledge can be shown. This method is academically anchored and can be a useful addition to the arsenal of police tracing tools.

Key words:

lie detector, memory detector, knowledge about the offender, police tracing

“De anatomie van de eed” (“The anatomy of the oath”)

“De novo apoA-I production: regulation and nutritional effects”

The risk of cardiovascular diseases can be lowered by increasing the "good cholesterol" (HDL) in our blood. HDL is directly formed by the protein apoA-I. The conclusion of this dissertation is that the saturated fatty acid laurine acid (a.o. present in coconut oil and dairy products) is possible a food component to increase the production of the apoA-I. Furthermore, the protein C/EBP¦Â can be an important factor in the regulation of apoA-I in liver and small intestine cells. Finally, the dissertation concludes that policosanols, substances in a.o. cane sugar, have no favourable effect on the metabolism of cholesterol.
The dissertation was printed with financial support from the "Nederlandse Hartstichting" and the "Fonds voor het hart".

Key words:

cardiovascular diseases, HDL, apoA-I; C/EBPβ; policosanols

“Venous Graft Remodeling. Novel Mechanisms and Pharmaco-modulation Strategies”

“Children with cryptogenic localization related epilepsy: Clinical outcome.”

Children with cryptogenic localization related epilepsy (CLRE) have epileptic attacks for which no cause can be found; about one third of the children with epilepsy have this type of epilepsy. Epilepsy influences the development of the neuropsychological functions: the school developments and the behaviour. The neurological and neuropsychological development of a group of children with CLRE was studied. 
The group is very mixed, but then CLRE cannot be compared with other types of epilepsy. Therefore CLRE deserves more attention from researchers. Because of the possible effects on the further development each child and its parents should be supported in a multidisciplinary way. 

“Children with cryptogenic localization related epilepsy: Neuropsychological outcome.”

Children with cryptogenic localization related epilepsy (CLRE) have epilepsy of which the cause is unclear. Their attacks start at one point in the brains. 
Until now, very little was known about the course of CLRE. This research shows that there is a considerable chance that children with CLRE reach a reasonable attack control (attack reduction or disappearance). However, this can take a while. In that period, the cognitive functioning, the behaviour and the school results can be negatively influenced, which can subsequently have a considerable (negative) influence on the further development of the child. To prevent this, it is very important that the child is examined, supported and followed in a multidisciplinary way as soon as possible after the start of the epilepsy. 

Key words:

epilepsy, CLRE, neuropsychological course, children

“Protein supplementation as a dietary strategy to improve glycemic control in type 2 diabetes”

This dissertation shows that many patients with type 2 diabetes ( "adult-onset diabetes") who receive medical treatment can still unnoticed suffer from dangerously high concentrations of blood glucose concentrations. The combined intake of carbohydrates with a protein mixture (protein hydrolysate/amino acid) not only leads to an increased insulin production, but also to an increase in the muscular tissue production in people with type diabetes. 
People who have had type 2 diabetes for a longer time already, produce more insulin by the consumption of extra protein as a result of which the blood glucose concentrations after a meal are decreased. This can have positive effects in the fight against diabetes-related complications. 

Key words:

protein consumption; type 2 diabetes; hyperglycaemia; muscular tissue production

“The Politics of European Union Health Policy-making”

EU health policy is paradoxical. Harmonization of legislation in this field is impossible, because financing and organization of health care systems are national competencies where "Brussels" has no role. This research shows that the rules of free trade are sometimes (mis-?)used as a legal basis for European bills in the field of health policy. There is a risk that public health or health care take second place and economic considerations first. This is also determined by the question which Directorate-General (Enterprise or Health) of the European Commission is responsible, the role of lobbyists and the strategic use of the subsidiarity principle (what can be done by a lower administrative body, may not be carried out by a higher institution). 

Key words:

EU decision-making; health policy

“Top Management Team Impact on Organizations: Determinants from inside and outside the boardroom”

Top Management Teams (TMTs, in the Netherlands often designated as 'Raad van Bestuur') are expected to make a difference for their organizations. This dissertation, at the crossroads of the fields of management and psychology, deals with the question how TMTs can have such an impact.The results indicate that the determinants of TMT impact lie both inside the boardroom, in the team's internal processes and states, and outside the boardroom, in the interface of TMT and middle managers. The findings have implications for practicing top managers, trainers, consultants and team coaches that want to enhance the impact of a TMT on its organization's performance.

Key word:

impact TMT’s

“Suum cuique?-enkele opmerkingen over de rechtsmachtverdeling tussen bestuursrechter en burgerlijke rechter”

“Essays on Law and Economics of State Aid”

The competition policy of the European Community has undergone extensive reform during the past decade. Competition rules have been modernised and simplified and enforcement has been decentralised. The most significant aspect of modernisation has been the introduction of a more rigorous economic analysis, both in the areas of anti-trust and state aid. The Community system for the control of state aid has been effective in restraining the propensity of Member States to subsidise their firms for strategic or political reasons. It has prevented significant distortions to cross-border competition. But it is not a perfect system. Too much aid has been allowed and the granting of illegal aid is not penalised vigorously enough.

Key words:

state aid; anti-trust; competition; European Community

“Psychopathic traits in Dutch adolescent offender and community samples: relationships with gender, age, institutional misbehavior, substance use and interpersonal style”

Psychopathy is a personality disorder that is marked by interpersonal (egocentricity, manipulation), affective (superficial emotions, lack of empathy) and behaviour characteristics (impulsivity, irresponsible behaviour) that are a risk factor for criminal and violent behaviour. Psychopathic traits often already manifest themselves in youth and early intervention is only possible with the earliest possible identification. This dissertation focuses on the Psychopathic Checklist: Youth Version (PCL:JV), a tool for diagnosing psychopathic traits in adolescents. The research shows that this tool can be reliably used by trained professionals. The PCL:JV is strong predictor of unacceptable behaviour in a judicial institution, in particular of physical violence. The research also found interesting differences in the manifestation of psychopathic traits in girls and boys. 

“Confronting smokers with previously undetected airflow limitation for smoking cessation”

COPD (or chronic bronchitis and pulmonary emphysema) is a common serious lung disease that is mainly caused by smoking. Especially for smokers with COPD it is of vital importance that they quit smoking. The purpose of this study was to investigate if more people quit if they are early traced and confronted with COPD. Over 300 smokers participated in the experiment. In the long term, the confronting approach turned out not to be better than a standard treatment; after 12 months only 11% was still non-smoker. The high relapse indicates how difficult it is for smokers to lose their addiction.

Key words:

smoking cessation, COPD (chronic obstructive pulmonary disease)

"Preferenties ¡­ referenties" ("Preferences¡­ references")

“Psychological Predictors and Treatment Outcome in Chronic Pain”

This dissertation makes a first step to the identification of specific psychological factors that can have an influence on the treatment outcome in chronic pain patients. Literature study shows that depression, catastrophizing (exaggerated negative thoughts about pain) and the fact that the pain is beyond control, have a negative influence on the treatment. The results of this study partly endorse these findings. Depression is an important predictor of the effectiveness of a medical treatment (without multidisciplinary approach or psychological treatment) in chronic pain patients; depressive patients have fewer results from the treatment in the field of pain reduction and improvement of quality of life. These results are an important step in the process of optimizing the treatment of chronic pain patients. 

Key words:

chronic pain, psychological predictors

“Effects of Experimental Febrile Seizures on the Developing Brain”

Febrile seizures are a kind of epileptic attacks that are provoked by high fever in young children. The febrile seizures themselves are mostly innocent, but the risk of the development of epilepsy increases in a number of children that had febrile seizures. The results as described in the dissertation show that febrile seizures in an animal model disturb the brain development. The growth of new neurons is disordered and long after the febrile seizures there are still changes in the brain structure that can be measured by means of a brain scan (MRI). Also subtle behaviour changes occur. These results suggest that the disturbed brain development as a result of febrile seizures plays a role in the development of epilepsy. 

Key words:

febrile seizures; epilepsy

“Genetics of mood disorders: from pharmacogenetics to disease genetics”

Mood disorders are the most common severe adult psychiatric disorders. These disorders are influenced by both genetic and environmental factors. 
This dissertation deals with pharmacogenetics (the study of gene variants influencing drug response) to investigate the relation between gene variants and antidepressant response. Besides an analysis of newly reported gene variants on antidepressant response, the dissertation includes the first meta analysis ever of the most important gene for antidepressant response (HTTLPR).
The knowledge of genetic influence on mood disorders and drug response can be used to construct profiles of individuals characterized by specific risks. This knowledge will allow to possibly modulate the environment in order to minimize the negative impact of the individual genetic profile. This could also lead to a personalized medicine but also to a deeper knowledge of genetic influences on humans.

Key words:

mood disorders, pharmacogenetics

“High blood pressure and target-organ damage of the brain”

“Medicines for diseases of the Developing World: Innovation And Economic Policy”

This dissertation studies the difficult relation between the public and the private sector in the fight against poverty in third world countries. Firms expect to obtain a return on their investments, while poorer countries cannot purchase these new products. This dissertation presents an analytical framework for new financing methods for R&D. It studies the positive and negative effects of ¡®push-pull" mechanisms. It provides new insights in the relation between on the one hand company investments and technical, market-related and financial risks, and on the other hand economic incentives including patents that governments can use to support the development of new medicines against neglected diseases, and thereby improve the international welfare of the most deprived populations in the world. 

Key words:

armoedebestrijding, financieringsmethodes

“Corneal desiccation in rigid gas permeable contact lens wear”

Little research is conducted into dry eyes of wearers of form-stable contact lenses (previously called hard lenses). The results of this dissertation show that the blinking behaviour of wearers of form-stable lenses is less optimal than in non-lens-wearers (less complete blinks), and the least optimal in people with dry eyes. The dissertation also found that the tear volume on the eye was less in wearers of form-stable lenses than in non-lens-wearers. The conclusion is that it is best to strive for limiting the effect of the contact lens on both the tear film as the eye lenses. For this purpose, detailed information about the shape of the cornea is necessary. A relatively new technique, corneatopography, can help describe this shape and can contribute to the production of better lenses.

“Corporate Governance and Sustainability in Global Property Markets”​

“Efficiency of Dutch hospitals”

“From seeking health to finding healths”

Bigger isn’t always better. Cooperation and scaling up in sciences is seen as a way to realizing ambitious objectives. That is why in nutrition sciences large teams cooperate on genome analyses to contribute to healthy nutrition and to public health. The question is whether this objective is ultimately reached. The fact is that nutrition research itself generates standards for health. This research shows that in large-scale research many standards for health generate. Large-scale nutrition research produces many facts about the effects of separate substances on our body, but the opinions on what is healthy differ even more than before. In brief, large-scale research can be effective for the production of knowledge, but for understanding health, it is less effective.  

Co-financed by NWO

Key words:

research, nutrition, health

“Design of a competence-based assessment system for air traffic control training”

This dissertation describes the design, properties and evaluation of an innovative assessment system that has been implemented since 2003 by Air Traffic Control the Netherlands for simulator and on-the job training of air traffic controllers. Because the required competences for air traffic controllers are described, this has created a common idea of what coaches can expect of trainees in successive training phases. This has increased the objectivity of assessments. Coaches can better identify the trainee’s strengths and weaknesses and give better support. On the basis of the competences already in the selection it is possible to predict which candidates could acquire the complex skills of air traffic controller.  

Key words:

air traffic control, assessment systems

“Accounting for Trends”

Managers and investors want future-oriented information in the (external) reporting of firms. The use of momentum accounting makes value creation visible with a new financial ratio that works as a speedometer on the corporate dashboard. It appears possible to pronounce rather accurately on the development of the own capital in the future of companies that are listed on the Dow and the AEX. In this study, the Dow Jones index is correctly predicted with spectra map analyses. The development of the own capital of companies can be followed and predicted on the basis of models that were developed in this study.

Key words:

momentum accounting, spectra map, future-oriented information, AEX, Dow Jones index

“Cancer Rehabilitation”

A cohort study of cancer patients with physical and psychosocial complaints after their medical treatment showed that a group rehabilitation programme with physical training and psychosocial theme meetings had positive effects on the quality of their lives.  On the basis of suggestions for improvement of these patients, two new group programmes were developed: a physical training programme and a programme that consists of this physical training as well as psychosocial training. Immediately after rehabilitation, both the participants of the physical training as the participants of the combined training reported greater improvement in quality of life than those who did not participate in rehabilitation. Nine months after rehabilitation these improvements still applied. Since there is no difference in effectiveness between physical training and combined training, and physical training involves less time and lower costs, this could be included in the standard oncology care. 

Key words:

cancer, rehabilitation

“Over de kwaliteit van detentie” (“On the quality of detention”) 

“D-optimal designs for prospective cohort studies”

Many researchers are performing a study in which subjects are measured repeatedly over time. Purpose is e.g. to study the change in quality of life over time after a severe traffic accident or how patients recover in time after some medical treatment. Such study may be expensive due to large amount of subjects and number of measurements for each subject. Therefore, careful planning is necessary to minimize the costs and still obtain reliable results. The thesis deals with planning of a study in which subjects are measured repeatedly and gives solution of the optimal number of groups of subjects, the optimal number of measurements per subject, and when should subject be measured. A computer program is developed to assist researchers to addressing these objectives.

The project is supported by the Care and Public Health Research Institute (Caphri), Maastricht University. 

Trefwoorden:

Optimal designs, cohort studies

“Reflex or Reflect ? Implicit and explicit cognitive processes and early intervention in adolescent alcohol use”

Traditionally, intervention programmes are aimed at pointing out the damages of alcohol use. However, it is naïve to think that adolescents drink because they cannot sufficiently consider the pros and cons. This dissertation shows that the drinking behaviour of adolescents is influenced by both resolute rational considerations and more automatic associations with alcohol (for example: alcohol – cheerful). Moreover it turns out that especially adolescents with a lower executive control have their drinking behaviour largely determined by these automatic processes, whereas adolescents with a higher executive control primarily drink resolutely. In the development of new interventions more attention should be given to the influence of these automatic processes. 

Key words:

adolescents, alcohol use, prevention

“Marketing x Financiering = Product met Hoog Rendement en Laag Risico Profiel”

“New developments in diagnosis and treatment of deep vein thrombosis”

This dissertation describes besides studies of the treatment of thrombosis also diagnostic studies. With a clinical decision rule and a point of care D-dimer test, general practitioners can safely, efficiently and cost-effectively exclude a suspected thrombotic leg in 50% of the cases. These are the conclusions of the AMUSE-research that was jointly conducted by the universities of Amsterdam, Maastricht and Utrecht. This diagnostic strategy has been   included in the new GP guideline ‘deep vein thrombosis’.  

This research was financed by ZonMW

Key words:

thrombosis diagnosis and treatment

“Visual outcome and patient satisfaction after corneal and Refractive surgery”

This dissertation studies two surgical interventions that correct the visual strength of the eye: the eye laser treatments that correct low to moderate myopia, and artificial lens implantation techniques that correct moderate to higher myopia.  The patient satisfaction and the subjective quality of the vision were high after the treatments. Statistical analysis showed that also the objective vision sharpness remained high. 
Furthermore, the dissertation stresses the importance of extensive information and of standardization of various studies in the selection of suitable candidates, such as measuring the pupil size, optical failures and the number of living cells of the innermost layer of the cornea. One of the conclusions of the research is that when strong selection criteria are used, the majority of the treated patients are very satisfied with the result of the surgery. 

Key words:

myopia, vision correction

“Fracture prediction in primary care: more than bone alone”

Also due to the ageing of the population bone fractures have become an increasing health problem. The costs and the mortality related to bone fractures increase considerably. It is therefore of medical and social interest that bone fractures can be predicted. With the help of the three predictors (1) an earlier bone fracture, (2) osteoporosis, and (3) age, the 10-year risk of bone fractures in post-menopausal women of 50 years and older can be determined. The most important predictor is a recent bone fracture. Without preventive treatment post-menopausal women suffer 1 out of the 4 next bone fractures within 1 year and 1 out of the 2 next bone fractures within 5 years after a first bone fracture. 

Key words:

bone fracture, risk prediction

“An Inevitable Reference, an Inimitable Model: American Legal Culture and Globalization”

“Die Gesellschaft mit beschränkter haftung in Europa; Eine rechtsvergleichende Studie zum Recht der GmbH in Deutschland, den Niederlanden und Frankreich”

In the aftermath of the European Court of Justice's (ECJ) landmark decisions Centros, Überseering and Inspire Art, implementing the freedom to choose the applicable corporate law through the choice of a corporate seat that is independent from its real seat, a regulatory competition in company law has started in the EU, entailing company law reforms in a number of EU Member States, among others in France, Germany and the Netherlands. Glozbach’s thesis compares and examines the applicable and reformed company laws of France, Germany and The Netherlands taking also into account the progressive European legislation in that field of law.

“Alcohol consumption as a risk factor for colorectal cancer; An epidemiological study on genetic susceptibility and molecular endpoints”

Within the Netherlands Cohort Study into nutrition and cancer (NLCS) various aspects of the relation between alcohol intake and colorectal cancer has been studied.  It turns out that a daily intake of at least three alcoholic drinks leads to an increased risk of colorectal cancer; the type of alcohol appears not to determine the risk increase, but the total quantity of consumed alcohol. 
The results of the molecular studies suggest that the way in which alcohol can lead to colorectal cancer goes via a more general mechanism than via causing deviations in genes. Studied was also whether the degree of alcohol decomposition in the body (that is genetically determined) has an effect on the relation between alcohol intake and colorectal cancer. However, no unambiguous result was found there. The research results support the current guidelines for safe alcohol use as recommended by the National Health Council.  

Key words:

Alcohol consumption, colorectal cancer

“A qualitative study on the effect of lymphatic filariasis on women: experiences, needs, and implications for lymphedema management programs”

“Economic Evaluation of Change in Clinical  Practice: Methods for Informing Decisions  about Guidelines and Implementation Strategies”

Implementatie van klinische richtlijnen om de zorg voor patiënten te verbeteren, vereist economische evaluatie. Deze evaluaties wegen de kosten af tegen de winst in gezondheid.

In dit proefschrift zijn evaluatiemethoden ontwikkeld om te bepalen of er in implementatieactiviteiten moet worden geïnvesteerd en wat de maximale investeringsruimte is. Met behulp van deze methoden kan bovendien worden vastgesteld of verder onderzoek naar zorgverbetering, bijvoorbeeld door de ingebruikname van richtlijnadviezen voor medisch handelen, waardevol is.

Als belangrijkste conclusie geldt daarbij dat het beter is om integraal in plaats van afzonderlijk te beslissen over investeringen in implementatie, onderzoek en patiëntenzorg.

“The principle of numerus clausus in European Property Law”

This dissertation studies the differences and similarities in property law in the Netherlands, Germany, France and England. Property law concerns rights that for example a private person or a bank has regarding everyone, such as for example property and the right of mortgage. Central is the numerus clausus principle that limits the creation of these rights. One is not at liberty to simply make new rights regarding everyone. This study shows that the countries of the European Union all know this principle. The dissertation also makes proposals on how the European rules in this field could be formulated. From these proposals among others citizens could benefit, who want to acquire a house in another member state, but also companies and banks that operate across the borders.

“Nitrogen metabolism and hepatocellular injury during liver resection”

After an operation in which part of the liver is removed because of (malignant) tumours the liver function has to increase per gram of liver tissue to maintain the total liver function. In the case of insufficient remaining cell mass liver failure can occur. There is no good predictor of the adaptability. This dissertation shows that the total quantity of nitrogen in the blood can be a measure for the functional capacity of the liver. The dissertation also demonstrates that anoxia of the liver does not cause extra cell loss during the operation if its duration is limited. This may be connected with the intake of anti-oxidants and the production of stress proteins.  

Key words:

liver resection, amino acids, cell injury, glutamine, arginine

“Tracing Bipolar Disorder to its Developmental Origin in the General Population”

A bipolar disorder (before: manic-depressive disorder) is characterized by the repeated occurrence of episodes with very black (‘depressive’) and pathologically elated (‘manic’ or ‘hypomanic’) moods. This research shows that no less than 7.6% of adolescents have gone trough manic/hypomanic episodes (the greater part of which is not known to assistance), and that 37.0% of the adolescents suffer from ‘subclinical symptoms’; light expression of abnormal euphoria.  The disorder usually starts before the age of 22. Adolescents with subclinical symptoms run a greater risk of developing the disorder, especially is they have had the symptoms for a longer period already. Mania during adolescence therefore appears often a ‘normal’ and ‘passing’ development phenomena; you only become a patient if you get stuck in the mania. 

“Pattern Recognition of Brain Signals”

“PREVention of Asthma in genetically Susceptible Children (PREVASC)?”

“Disgust in specific phobias; a dirt road to anxiety disorders”

In this dissertation the role of disgust in several phobic fears (particularly spider and blood phobia) was studied. People who are easily disgusted of all kinds of things appear to run a higher risk of developing a spider or blood phobia. In the case of blood phobia the ‘fear of disgust’ also turned out to play a role. Because disgust is accompanied with physical reactions that can protect man against diseases, excessive avoidance behaviour is possibly a way to prevent (whether or not imaginary) contamination. The expectation that unpleasant consequences will follow the confrontation with a phobic stimulus (spiders, blood) appears in phobic persons not only to be related to a physical damage but also to contamination. Heart beat deceleration and lowering of the blood pressure appeared to be no part of the physiological disgust response. Therefore, the prevailing view that the characteristic faint at the sight of blood is a consequence of the disgust reaction is incorrect.  

“Assessing Induced Technology: Sombart’s Understanding of Technical Change in the History of Economics”

“Pro-active Medical Information Retrieval”

Central in this research is the question if it is possible to automatically provide doctors with relevant patient-related literature. In this context the computer system Medical Information Retrieval Agent (MIRA) was developed, which on the basis of electronic patient data independently formulates medical questions. Subsequently the system uses these questions as a starting point for searching medical literature. Evaluation of MIRA shows that the automatically formulated questions in most cases are indeed relevant for doctors. This applies to a lesser degree also to the literature that is found on the basis of the questions. By automatically informing doctors of recent medical developments MIRA could contribute to an improvement of medical care.  

Financed by NWO in the framework of the ToKeN-project MIA.

Key words:

information retrieval, medical literature

“Risk Management from a Microeconomic Perspective”

Risk management is of crucial importance considering the enormous financial risks our economy is exposed to. Inadequate assessment of risk played a crucial role in the current subprime mortgage crisis as well. In this thesis we study how to measure risk properly.  Imagine that there is a head-office setting risk limits for some divisions. We analyze how to allocate the risk diversification benefits by applying game theory.  We show that the head-office can always allocate risk in a stable way, and the less is the uncertainty regarding the whole firm, the higher level of discretion the head office has. 

Key words:

risk measures, microeconomic theory

“In Search of the Perfect Citizen ? The intersection between integration, immigration and nationality in the EU”

“Economic aspects of treatment for Borderline Personality Disorder; theory versus practice”

A borderline personality disorder (BPS) is a serious psychiatric disorder, for which until recently no really effective treatment seemed available. Recently it was shown that two new ambulant psychotherapies, the so-called Scheme Therapy and Transference Focused Psychotherapy (TFP),  are effective in fighting borderline symptoms. This dissertation elaborates on earlier studies by linking the costs that occur in both therapies to the effects. Not only the costs of the psychotherapy and for example hospitalizations and medication are taken into account, but also non-medical costs such as volunteer aid and productivity loss in paid or unpaid work. It turns out that the non-medical costs are much higher than the costs within the medical circuit. Although the quality of life considerably improved with both therapies, there was no difference between the groups in that area. The main conclusion is that Scheme Therapy, compared to TFP, in all probability is the most cost-effective treatment strategy. 

Key words:

borderline, cost-effectiveness therapy

“Sequential Auctions and Alternating Price Competition”

A central theme in economics is the functioning of markets. The field of industrial organization studies the strategic behaviour of companies, the structure of markets, and the interaction between those two. This dissertation contains research in the field of industrial organization. In the first part of the dissertation sequential auctions are studied. Bidders benefit from scale advantages if they win several auctions and it is shown that this has some negative consequences. Bidders possibly suffer losses and their average profit decreases as the synergy possibilities increase. 
The second part of the dissertation studies price competition between companies in an oligopoly. The companies can take turns in adjusting their prices by rigorisms. Shown is, among others, that prices fluctuate in a countercyclical manner. 

“The use of price and non-price performance measures in debt and compensation contracts”

Performance measures are used to evaluate a firm and/or the management of that firm. This dissertation shows among others the importance of the annual bonus that is positively valuable for both management and stockholders. Moreover, the results show that a detailed specification of the reward system of the CEO is important for both existing and potential investors. The Dutch corporate governance code (Tabaksblat code) urges firms   that are quoted on the Dutch stock exchange to submit this information in the explanatory memorandum of the annual account. This dissertation illustrates the importance of the code stipulations and the enforcement of the remuneration chapter of the Tabaksblat code.

Key words:

Tabaksblat code, performance measures, management

“Analysis of gene expression in the Leishmania Life Cicle:Leishmania ( Viannia) braziliensis and Leishmania (Viannia) peruviana model”

“Criteria for Assessment of Patient Competence. A conceptual Analysis from the Legal, Psychological and Ethical Perspectives”

In view of their self-determination patients have the – in the Netherlands legally established – right to decide whether they want or do not want to undergo a treatment that has been suggested by their healthcare assistant.  The condition for the validity of such a decision is that the patient competent is regarding the matter. There is great interest in concrete criteria by means of which competency can be assessed in patients whose competency positively established.
Welie’s research shows that it is not possible to set good criteria that are both valid and concrete and that an assessment of competency has often more disadvantages than advantages. When an assessment is really necessary, Welie recommends the so-called “recognisable reasons” approach.

Key words:

competency, criteria, self-determination

“Looking beyond the fracture. Prevention in fracture care”

Osteoporosis, or bone decalcification, increase the risk of fractures. Several other risk factors, however, also play an important role, such as disorders that contribute to the risk of a patient falling.  
Out of a group of patients that were earlier treated for bone fractures, no less than 11% returned within 2 years with a new bone fracture.  As a result of that the ‘Fracture and Osteoporosis policlinic was set up in the MUMC+. With the help of a special fracture nurse and systematic application of guidelines for osteoporosis and fall prevention it turned out possible to recognize and treat many risk factors. Consequently, the risk of a new bone fracture decreased by 40% within one year compared to a large group from the period before preventive measures were taken. 

Key words:

osteoporosis, fall prevention

“Human Thermoregulation. Individual differences in cold induced thermogenesis”

“Urinary Incontinence in Nursing Home Care”

“Translational Control during Hypoxia: Consequences for gene expression and hypoxia tolerance”

“Cardiac Mechanomyopathy Integrating the Picture from Cell to Beating Heart”

“Cellular adaption to hypoxia and reoxygenation through gene specific mRNA translation”

“Blood test ordering for unexplained complaints in general practice.The feasibility of a watchful waiting approach”

Every day, general practitioners see patients during their office hours, whose diagnosis they cannot immediately make. We call these complaints unexplained. In the case of unexplained complaints, GPs often order blood tests, but this has various drawbacks. The fact is that 90 percent of the unexplained complaints automatically pass away and conversely it is not always possible to trace a disease by means of blood tests. That is why it is a good alternative to wait a few weeks and only order blood tests if patients continue to have complaints. Our research shows that this strategy is feasible and does not lead to dissatisfied or worried patients. Neither do patients start looking for alternatives, such as alternative healers. 
Subsidized by: College voor Zorgverzekeringen (CVZ)

“Ze komen!” (“They are coming!”)

“Hydroxytyrosol. A versatile antioxidant from olive oil”

“Protein metabolism and nutritional requirements in critically ill children”

In critically ill children a deterioration of the nutritional condition often occurs quickly. This has a harmful influence on the recovery, the duration of the hospitalization and on the growth and development. The cause of the deteriorated nutritional condition is an accelerated decomposition of particularly body proteins in combination with insufficient food intake. In this dissertation by means of various methods the protein decomposition and composition in critically ill children was studied in relation to the quantity of protein in the nutrition. The research showed that a higher protein intake resulted in a decrease of the protein decomposition and an improvement of the nutritional condition. The results emphasize the great importance of adequate nutrition for these children.

Key words:

nutrition, ill children, protein intake

“Changes in Psychosocial Work environment and Health: A Mutual Relationship”

Changes in the psychosocial work environment, such as changes in work pressure or work pattern, occur very often and lead to substantial changes in the mental health of employees. Conversely, changes in mental health also lead to changes in the psychosocial work environment. These are the conclusions of Lore De Raeve in her dissertation “Changes in psychosocial work environment and health: a mutual relationship” for which she hopes to earn her PhD from Maastricht University on 19 September. For the research data from a large prospective cohort study among 12.140 employees were used. The innovative methodology brings the research a step closer to the cause-consequence relationship between the psychosocial work environment and the mental health of employees, as a result of which it can offer leads for prevention and intervention. 

Key words:

labour, work environment, health

“Promoting HIV-testing. The systematic development of an online HIV-prevention intervention for men who have sex with men.”

“A clinical analysis of Financial crises”

“Essays in Behavioral Economics”

Traditionally economics is based on very narrow presumptions about human behavior, namely selfishness. In the last 20 years, however, experimental research has accumulated overwhelming evidence that is at odds with these classical assumptions. It has been shown that people very often care about the distributional consequences of their actions and intentions.
Against this background, in this thesis the impact of broader models of human behavior on decision making and human interactions is studied, for example the impact of indirect reciprocity on human relationships. If educational expenditures of parents into children depend on grandparents' investments into the parent’s education, then private educational spending is inefficiently low and should be supported by the state. This finding stands in contrast to earlier results that show that parents might invest optimally into the education of their children out of pure altruism or strategic transfer motives.

“Prodromal Alzheimer’s disease in subjects with Mild Cognitive Impairment: Predictive and diagnostic aspects.”

“Essays on Asset Market comovements”​

“Treating depression in chronically ill elderly. The evaluation of a Minimal Psychological Intervention.”

Elderly people with a chronic disorder often also suffer from mood problems. This can have a quite negative effect on the health and wellbeing of elderly. This dissertation shows that a short-term psychological approach, based on cognitive behaviour therapy and self-management, carried out by a nurse in primary health care, can decrease complaints of depression and can increase the quality of life in elderly with diabetes and/or a chronic lung disorder (COPD). A study into the cost effectiveness also showed that there is a good chance that this approach in practice does not increase the costs. Implementation of this approach in the current healthcare for chronically ill elderly can improve the quality of care for this group.  

Key words:

chronically ill persons, cognitive therapy

“Toekomstverkenning: ambities en de praktijk. Een etnografische studie naar de productie van toekomstkennis bij het Ruimtelijk Planbureau (RPB).”

“Verpleeghuisgeneeskunde al langer officieel erkend; maar ook herkend en gekend?”

“Classical Liberalism and International Relations Theory. Hume, Smith, Mises, Hayek and International Society”

Not all liberals are starry-eyed believers in eternal peace. The prominent classic liberals Hume, Smith, Mises and Hayek have completely different ideas, in contrast with this common image in the international relations. This dissertation is a first attempt to correct this image. Partly following on the ideas of Hugo de Groot, they see the state as the most important actor in world politics. International order develops in correlation with the balance of power and international law, with an important role for just warfare.  Free trade is good, but it brings no peace; development aid should be abolished. According to these classic liberal thinkers, the European Union could become a federation after radical reform, but many other international governmental organizations are redundant. 

“Surgical Excision and Mohs Micrographic Surgery for Basal Cell Carcinoma: An evaluation from different perspectives”

“Measuring and Managing Poverty Risks”

The dissertation “Measuring and managing poverty risks” studies technical issues on the measuring of poverty and the characteristics of people who are poor; it also compares the United States with the countries of the European Union. The study investigates which are the policy implications of technical (measuring) choices. According to some calculation methods, for example, there is less poverty in the Czech Republic than in the Netherlands and very different people are poor there. The study explains among others that the policy in the Netherlands and in other countries can best be inspired by the use of different measuring methods next to each other.  

Key words:

poverty, poverty policy, social security

“Role of Myeloperoxidase in Lung Inflammation”

Excessive inhaling of dust particles can lead to the development of lung diseases. The objective of this PhD research was to study the response of lung epithelium cells on neutrophils, inflammation cells. The focus was on the role of the neutrophil protein myeloperoxidase during the inflammation process. The results show that myeloperoxidase contributes to the development of acute inflammation, but that other mechanisms are also responsible for the development of chronic inflammation. Furthermore it shows that the reaction of lung epithelium cells during inflammation also depends on the cause of the inflammation. Therefore, it is important to take the cause of the inflammation into account for the development of therapies against lung diseases. 

Key words:

 myeloperoxidase, neutrophil, lung epithelium

“Radiologie in de lift.”

“Home visiting program for older persons with poor 
health status”

“Multidisciplinary fall prevention; effects, feasiblility and costs”

“Lost in fragmentation; schema modes, childhood trauma, and anger in borderline and antisocial personality disorder”

“Verbal learning in school-aged children and the influence
of child-related factors, test-related factors and natural context”

“Post transcriptional gene silencing and peptide microarray as a way to perform drug target validation”

“De invoering van International Financial Reporting Standards in de Europese Unie – een tussenbalans”

“UMA TORI; development and evaluation of an STI/HIV-prevention intervention for women of Afro-Surinamese and Dutch Antillean descent”

“www.mychronicdisease.org – naar 
samenhangende, de patiënt activerende en ondersteunende
chronische zorg-”

“Rectal Cancer Imaging; staging and restaging”

“The relationship between R & D Partnership formation, social embeddedness and innovative performance”

“For your ears only”. Quality of telephone triage at out-of-hours 
centres in the Netherlands”​

“The Annexin Code; Revealing Cardiovascular Disease”

Today, it is clear that cardiovascular diseases are preceded by specific biological changes that patients don’t notice. Molecular imaging is a new imaging technique to detect these changes, which makes it possible to notice and combat cardiovascular diseases at an early stage. Bas Kietselaar studied the use of molecular imaging with Annexin A5.  He discovered that Annexin A5 (a type of protein) first of all helps predict deterioration in patients with a widened heart muscle; secondly is valuable in the detection of endocarditis (bacterial inflammation of the heart); thirdly can be used for diagnosing vulnerable plaques in patients with a TIA (‘light stroke’); and finally that Annexin scans are useful in the assessment (benign or malignant) of mass in patients’ hearts. 

“The use of risk tables for cardiovascular prevention in general practice; evaluation of decision support for doctors and patients”

To find out if you run an increased risk of cardiovascular diseases, the general practitioner uses a risk table. GPs find the use of this table difficult, but also talking about risks is not easy. Many people overestimate or underestimate their risk, or they have false expectations about what the GP can do with regard to prevention of cardiovascular diseases. The research shows that a decision support for the patient, in which the risk and the various possibilities for risk reduction are explained, appear valuable for the involvement of patients in the decision process of their cardiovascular risk management. This research was partly subsidized by the ‘Nederlandse Hartstichting.’

Key words:

prevention of cardiovascular diseases, decision support

“Triggers for food intake regulation; sensory and metabolic effects of specific food components”

Various substances in our food influence our eating behaviour, because they reduce the hunger sensation. The studies described in this dissertation show that specific energy-low substances in our food can influence in the short term the underlying mechanisms of hunger sensation by means of sensory (taste related) and metabolic effects. These findings suggest that these effects of specific energy-poor substances in our food can be used in various elements of eating behaviour. This could, for example, contribute to the reduction of appetite during a meal or between meals.

“Novel methods for ocular drug delivery”

“Bestuurlijke verankering van innovaties in de penbare gezondheidszorg; lessen uit de casus Hartslag Limburg”. (‘Administrative embedding of innovations in public health care; lessons from the case ‘Hartslag Limburg’)

Health promotion has the best results at the local level. Necessary are programmes that are carried out in lasting cooperation of Area Health Authority, general practitioners, hospital, municipality and, if necessary, other institutions. The dissertation of Erik Ruland, based on the lessons from Hartslag Limburg (1998-2004), shows that a combination of firm municipal control, leadership and sound operational change management is crucial for lasting cooperation. As soon as municipality and Area Health Authority fail in this concerted action, the administrative embedding of cooperation is at risk. That can be a threat for the continuation of programmes for health promotion, even when these proved successful. The dissertation makes recommendations for the improvement of the concerted action in practice. 

Key words:

health promotion, Hartslag Limburg

“Technologie, mij(‘)n zorg ! Over langdurende zorg, technologie en innovatie.”

“Home Nursing in Europe”

Europe’s population is ageing. This dissertation describes the various patterns of professional and informal care to elderly people in Denmark, France, the Netherlands and Germany and the way these countries re-spond to the changing demand for car for the elderly. Particularly the profession and the domain of home nursing are at the centre of the research. Specific developments and problems in home care and family care are described from a wide sociological and cultural perspective and related to the various systems of health care and the relations between professions and the sectors within those, the role of the family and socio-cultural and political standards and values regarding health and disease.

Key words:

home nursing, home care, family care, professionalisation, Europe

“Bariatric surgery and its effect on the metabolic and inflammatory aspects of morbid obesity”

“Clinical implications of acute exacerbations in COPD”

Chronic obstructive pulmonary disease (COPD) is a chronic disease of the bronchial tubes that involves complaints of tightness of the chest, coughing and bringing up phlegm.  COPD patients regularly have exacerbations: periods when these complaints are more serious than otherwise and sometimes hospitalization is necessary.  This dissertation studies mechanisms that lead to exacerbations, as well as the clinical consequences of these disease episodes. The main conclusions are that increased inflammation values in the blood lead to an increased risk of exacerbations and that these inflammation values in the blood rise in the case of exacerbations.
Established was also that acute exacerbations have a bad prognosis: 8 % of the hospitalized patients die during the hospitalization and 25 % die after 1 year.

Key words:

COPD, acute exacerbations, systemic inflammation

“Educating the self-critical doctor; using a portfolio to stimulate and assess medical students’ reflection”

It is of great importance that doctors critically reflect on their own performance. That is not only shown in scientific research, but also in ‘failures’ of doctors and hospital wards. Good care demands doctors with a realistic view of their own knowledge and abilities, who seriously think about their communication with colleagues and patients. The Maastricht faculty of medicine has developed a so-called portfolio method that helps students to critically reflect on themselves early in the programme and to address ‘rude and plump’ behaviour. An article based on this method was published among others in the British Medical Journal of 11 April 2008.  

Key words:

Reflection, medical education, doctor-patient communication

“Adaptive Active Vision”

Today, artificial intelligence is very strong in the field of activities that people find difficult, such as playing chess. Remarkably, considerably fewer successes were achieved in everyday activities, such as walking down the street. The reason for this is that we determine everyday actions in little time and found those on implicit knowledge. For his PhD research, Guido de Croon studied computer models that make eye movements to carry out visual tasks. That is ordinary for people; we move our eyes on average three times per second to obtain the right information from the environment. For a computer model this behaviour is hard to catch. Therefore, de Croon developed ‘adaptive’ models that learn themselves which actions are the best. The findings from this research can among others lead to a wider usability and autonomy of small robots.

Key words:

artificial intelligence, adaptive computer models

“An Empirical Investigation of Implicit Contracts”

Not all performances of organizations can be measured in objective parameters such as an annual report. Think for example of the degree of innovation. When a supervisory board takes these kinds of aspects into account in the evaluation of a president of the executive board, that is called a subjective evaluation. This dissertation studies the how and why of subjective evaluations, their influence on the degree to which the members of the supervisory board fulfil their governance task and the influence on innovation. The remuneration of CEOs in the USA shows that the use of subjectivity leads to strong incentives to raise the company value. Furthermore it shows that subjectivity is important when objective performance standards do not sufficiently reflect the ‘good behaviour’ of the CEO, such as his/her influence on the innovation of the company.

Key words:

supervisory board, subjectivity

“Vascular access for haemodialysis. A comparative study of brachial – basilic and prosthetic graft arteriovenous fistulas”

“Mental Capital: the economic significance of mental health”

“Juridisch Humanisme en costumiere acculturatie”

“Connectivity in the Visual System”

“Hypoxia, HIF and angiogenesis in atherosclerosis”

The tearing of atherosclerotic plaque (calcification in the arterial wall) is the cause of cardiovascular diseases and is also caused by small blood vessels (micro vessels) in the plaque. This dissertation studies the mechanisms that cause the growth of micro vessels in the plaque and the structure of the micro vessels. These studies show that cells in the plaque don’t receive enough oxygen, which causes the growth of the micro vessels. The micro vessels are not well formed and show structural defects. This defective structure causes inflammation cells and red blood cells to leak into the plaque, which can lead to plaque growth and rupture.

“A Collaborative approach to tailored whole-school health promotion”

Schools are fed up with the torrent of health projects. To help schools choose from the huge amount of health projects, the schoolSlag-method and schoolSlag checklist (both already applied at a national level) were developed, in cooperation with teachers and health promoters. The schoolSlag study shows that schools can receive support, tailored to their needs, for their health policy when – local, regional and national - institutions methodically cooperate with each other and with the school. With schoolSlag, GGD Zuid-Limburg challenges schools to create a healthy school together with pupils and parents and to use the best that institutions have to offer without making concessions to their educational core task.

“Werken aan heterogeen menselijk kapitaal”

“Microarray analysis of oxidative phosphorylation disorders”

Mitochondria generate the energy production of the cell. When there are defects in the mitochondrial DNA or in certain parts of the DNA in the cell nucleus, this often results in problems in the field of the energy household. This may cause serious diseases that are characterized by defects in all organs that need much energy. This dissertation describes the use of new DNA chip techniques in the study of these disorders. In almost one quarter of the patients a genetic diagnosis could be made with this technique. Moreover, a series of processes was identified that play a role in these disorders and possibly open new opportunities for the development of therapies.

Key words:

mitochondria, OXPHOS, microarray, mtDNA

“Bescherming tegen niet geinviteerde overnames en ongewenst aandeelhoudersactivisme; een politiek correcte en bedrijfsmatig effectieve benadering”

“Plantar pressure, diabetes and foot orthoses therapy. Studies on etiological, diagnostic and therapeutic aspects”

Foot complaints often occur, but in people with diabetes they require extra attention. To optimize diabetic foot care six studies were conducted for this dissertation. The differences that were found in diagnostics and (insole) therapy between and within professional groups of foot specialists (podotherapists, orthopaedic shoe technicians and orthopaedic instrument makers) are worrisome. One of the main results is that the use of special foot pressure measuring equipment can reduce the risk of foot wounds in diabetes patients with polyneuropathy (a nervous disorder). The research results offer the various professional groups and programmes of vocational education many useful handles to optimize diabetic foot care. The research was financially supported by the ‘Diabetesfonds’ and ‘ZonMs’. Additional support was offered by ‘Smeets Loopcomfort’ and ‘Spronken Orthopedie’.

Key words:

diabetic foot care, insole therapy, diabetes mellitus, foot pressure measuring equipment, polyneuropathy

“Intrathecal baclofen therapy in children with intractable spastic cerebral palsy; A Dutch national study”

The quality of life of children with untreatable spasticity as a result of brain damage can be considerably improved by treatment with intrathecal baclofen (ITB). Baclofen is a muscle relaxant that works on the spinal marrow level. Baclofen in tablet form badly passes the blood-brain barrier, which generates side-effects rather than effects. Baclofen can also be delivered directly into the brain fluid near the spinal marrow by means of a small pump in the abdominal wall via a catheter (intrathecal therapy). The Dutch national ITB study showed that ITB is safe and effective for children with problems as a result of untreatable spasticity. The main effects were reduction of pain and the fact that it became easier to attend to the children.

Key words:

children, serious spasticity, new treatment method

“Gedragsmechanismen achter overheidsinterventies en rechtsregels” (‘Behaviour mechanisms behind government interventions and rules of law’).

“Inequality, Networks and Exclusion: Distributive Decision.
Making in Small-scale Societies”

Using survey data, laboratory experiments with students and field experiments with poor farmers in Nicaragua (Central America), this dissertation studies the processes that are responsible for the continued existence of economic inequality in micro- societies. Poor people do not only have an inferior social network, but they are also less able to determine who represents them. As a result they receive a relatively lower share of the economic means that are divided by local representatives. When they protest against this situation, they are even more excluded by ‘their representatives. To combat such exclusion processes, policymakers should improve the social inclusion of this group in terms of their social network position and/or political representation.

Key words:

social exclusion, social networks

“Preclinical studies on the immune-modulatory effects of dietary oligosaccharides”

Oligosaccharides (short, non-digestible sugar molecules) naturally occur in mother’s milk and they have a positive influence on the bacteria in infants’ intestines. This dissertation describes the favourable effects of nutritional intervention with specific oligosaccharides on the immune system. Examples are: stimulation of the vaccination response, reduction of allergic symptoms and an inhibiting effect on viral infection. These pre-clinical results suggest that these specific oligosaccharides are not only able to positively influence the intestinal bacteria, but also the immune system of infants. By adding these oligosaccharides to infant nutrition the risk of allergies and infections is reduced, as a result of which the functionality of breastfeeding is more closely approached. 

Key words:

Oligosaccharides, infant nutrition, immune system

“Radiotherapy in non-small cell lung cancer”

De PET-scan (positron emission tomography) is a functional imaging technique. This dissertation first of all describes the biological meaning and the role of PET in the radiotherapeutic treatment of lung cancer. A comparative study shows that with the use of PET the size of the tumour and the location of affected lymph nodes can be precisely determined. The PhD candidate validated a PET-based module with which the tumour is automatically sketched in the preparation of radiotherapy. This allows a more efficient radiotherapy of non-small cell lung cancer. The PET-CT scan can also be used to monitor changes in the course of the radiotherapy and, if necessary, to adjust the treatment. Finally, the dissertation describes a theoretical model and the clinical use of individualized radiotherapy, in which for each patient the maximum dose is determined that the healthy organs of the patient can tolerate. 

Key words:

lung cancer, radiotherapy , PET

“Diabetic Foot Disease in European Perspective”​

“Serotonergic Vulnerability; experimental studies in the rats applying the method of acute tryptophan depletion”

“Verantwoord beleggen: de hype voorbij?” (‘Responsible investments: past the hype?’)”

“Smoothelins and smooth muscle contractility”

The contraction of smooth muscle cells is essential for a good functioning of various organs, such as the gastrointestinal system and the blood vessels. This dissertation studies the function of smoothelin, a protein that only occurs in smooth muscle cells. By means of various techniques it was shown for the first time that smoothelin is an important factor for the correct contraction of smooth muscle cells. The lack of smoothelins in the intestines causes among others a considerably slower bowel movement and in the blood vessels it can cause the development of high blood pressure. These results provide new insights in the functioning of smooth muscle cells and the possible involvement of smoothelins in smooth muscle cell-related syndromes.

Key words:

smooth muscle cells, smoothelin

“Peri-operative arginine metabolism in cancer”​

“Future health in a globalising world”

“Vita & Froet; the development and evaluation of two Interventions to promote fruit and vegetable intake among primary school children”

Eating sufficient vegetables and fruit prevents the development of cancer and cardiovascular diseases. Nevertheless, Dutch children eat too little vegetables and fruit. To stimulate children to eat more vegetables and fruit, two interventions were developed for primary schools according to Intervention Mapping: (1) free daily distribution of vegetables and fruit and (2) an age-specific teaching programme with activities for the parents. The effect study showed that both interventions were effective, both short-term and longer-term, in increasing the fruit consumption. Moreover, the free distribution also increased the vegetable consumption by children of ages 4 to 12 years and its implementation turned out easier.

Key words:

vegetable and fruit consumption by children

“Wie bang is kan niet wachten”

“Sustainable Energy Development under Uncertainty”

Electricity generation is the major source of CO2 emissions. It is important to understand how investment decisions are made in the electricity sector and how they can be effectively influenced by policy, since many OECD countries have to replace substantial portions of their electricity-generating capacity over the next 10-20 years. This thesis shows that technological change and volatile fuel prices alone are not sufficient to induce the investment necessary to stabilize cumulative CO2 emissions at a level considered as bearable in climate science. Furthermore, fuel price certainty stimulates investment into the concerned technology, while certainty about future technological improvements initially leads to less investment in modern capacity. Finally, nuclear energy could be a transition technology bridging the gap between the existing fossil-fuel-based system and a large-scale diffusion of renewable energy technologies.

Key words:

decision-making under uncertainty, energy economics, climate change policy

“A half full glass may seem fuller than a half empty one”

Is a glass half empty or half full? Some people mostly see challenges in life, others mainly threats. The literature speaks of a promotion orientation versus a prevention orientation. This difference is the basis for the four studies in this dissertation. It shows that if you address customers in a way that fits the way they approach life, this leads to more effective marketing results. For the recruitment of new members for a fitness club, for example, it is more effective to indicate to consumers with a promotion orientation that you feel better when you work out regularly. On the other hand it is more effective to approach people with a prevention orientation about the fact that regular workouts are healthy and can help prevent illness.

Key words:

effectieve marketing

“Law and Economic Analysis of the Precautionary Principle”

“Techniek, de vierde dimensie van het octrooirecht”

“In itinere”

“The effectiveness of an education and activation program in acute and sub-acute shoulder complaints presented in general practice”

Shoulder complaints appear to still exist in half of the patients six months after the first visit to the general practitioner. A new treatment, given a the start of the complaints, focuses on the one hand on the expectations of patients about their shoulder complaints and on the other hand on how they have dealt with the complaints in daily life (getting dressed, driving a car, cleaning windows). Previous research in people with for example back complaints showed that wrong ways of thinking and acting lead to a longer duration of the complaints. The effect of the new treatment was studies by means of an experiment. This experiment did not show a significant effect after six months. However, it turned out that those patients who expected the worst at the start of the complaints (catastrophize) actually recover less.

Key words:

Shoulder complaints, general practice, catastrophize

“The systematic assessment of the short-term risk for patient violence on acute psychiatric wards”

Violence is a serious problem in health care institutions, having negative consequences for staff and patients. The subject of the dissertation is patient aggression against others in acute psychiatric wards. The studies included in the dissertation are aimed to improve aggression related nursing practice. The studies relate (1) to the scope of the problem in acute psychiatry in Switzerland, and (2) to the development and application of a structured assessment of the short-term risk for violence among acute psychiatric patients. A structured short-time risk assessment proved to be a promising way to reduce violence in this area of care.

“Novel insights in the pathophysiology of insulin resistance; A molecular genetic approach”

The number of people with overweight explosively increases worldwide. Overweight often leads to type 2 diabetes and a disturbed fat metabolism. These are important risk factors for cardiovascular diseases. Because of minor genetic differences some people are more sensitive to developing for example overweight, type 2 diabetes or an increased cholesterol level. In this PhD research we studied among others the ATF6 gene in detail. This gene plays an important role in folding the proteins in the cell. We have shown that small variations in the ATF6 gene increase the risk of type 2 diabetes and a high cholesterol level. 

Key words:

Type 2 diabetes, Cholesterol 

“Hepatic steatosis in familial conmbined hyperlipidemia”

Cardiovascular diseases are the main cause of death in Western society. Well-know risk factors are smoking, high blood pressure and a high cholesterol and fat level. Familial combined hyperlipidemia (FGH) is a common hereditary disorder that is characterized by an increased cholesterol and fat level. In this dissertation we have shown that this hereditary predisposition is partly caused by a (three times) increased sensitivity to the development of liver fattening. The importance of this finding is supported by the appearance of a new medication for the treatment of liver fattening and therefore also possibly for the prevention of cardiovascular diseases.

“SAFE but SORRY; theory, assessment, and treatment of pain-related fear in chronic low back pain patients”

Fear of moving, the fear that activities are damaging for the back, and avoidance of activities contribute to the development and maintenance of chronic back pains. A cognitive-behavioural exposure in vivo treatment can lessen this fear. By carrying out increasingly more threatening activities patients experience they can do these without damaging consequences and in spite of their pain. This first controlled treatment study in four rehabilitation centres shows that exposure in vivo is more effective than a regular treatment in lessening the fear of movement and at least as effective in improving daily functioning. Exposure in vivo is a valuable addition to the existing treatment offer.   

“Prediction of hepatotoxic responses in humans: A toxicogenomics-based parallelogram approach”

Rat studies in vivo are not always representative for the effects that can be expected of hepatotoxic substances in humans. Alternatives for animal tests, in vitro experiments in liver cells, cannot give a complete prediction either.  With toxicogenomics-based techniques these effects can be better shown. In this dissertation on the basis of the so-called parallelogram approach results of rat studies and experiments in liver cells of rats and humans were combined. For this purpose the effects of known hepatotoxic substances on all genes and de resulting biological mechanisms were compared. The use of human liver cells turns out to be essential because rats and humans can react differently to hepatotoxic substances. Rat studies still appear necessary to bridge in vitro-in vivo differences.

Key words:

toxicogenomics, alternatives for animal tests

“Towards restraint-free care for psychogeriatric nursing home residents”

Restraints in freedom of movement, for example by means of bed rails, still often occur in the care for demented nursing home residents, among others to prevent falling incidents. However, freedom restraints have major disadvantages. The main purpose of this dissertation is to make a contribution to restraint-free care for this target group. This research shows that a training programme and the use of a nurse in a consultative function are not enough to decrease as well as prevent the restraint of freedom. It also turns out that the main factor to apply restraint of freedom is the mobility of residents. A connection with work pressure was not found. Therefore, in initiatives to decrease the restraint of freedom characteristics of residents should be at the centre, such as the individual needs and the stimulation of the mobility.

Key words:

restraint of freedom, nursing home care

“Vital imaging of large arteries using two-photon laser scanning microscopy: focus on the arterial wall”

Changes in the qualities of the arterial wall can lead to diseases such as atherosclerosis. In spite of the current knowledge on blood vessels and atherosclerosis the possibilities of studying structural as well as functional qualities at the cellular level are still limited. An improved insight in structural and functional qualities of the arterial wall can possibly lead to more knowledge about (the development of) atherosclerosis. In this dissertation the ‘two-photon laser scanning microscopy (TPLSM)’ was used to visualize at the cellular level structural and functional arterial wall qualities. The described methods offer a new perspective on the qualities of large blood vessels and contribute to new insights in diseases such as atherosclerosis. 

Key words:

arterial wall structure, atherosclerosis, TPLSM

“Adaptive remodeling of cardiomyocytes under stress”

Patients with coronary vascular complaints show a drop of blood flow and a decrease of oxygen transport to the heart muscle tissue. This can lead to a partial return of adult heart muscle cells to an earlier foetal stage. An example of this programmed cell survival is hibernating heart muscle tissue. In this dissertation, detailed information was gathered on the structural changes of heart muscle cells in various models of hibernation. Also specific protein markers were registered that give information about the heart cell function. Important findings are the discovery of a new form of intercellular communication and the influence of passive stretch (stretching of the heart muscle) on the heart muscle cell.

Key words:

hibernation, cell survival

 “The Place of Play; on toys, Technological Innovations and Geographies of Play”

This dissertation studies the changing relations between consumers and producers in the context of toys and play. Players increasingly contribute actively to game worlds and toy products. Players create, for example, new contents for computer games and they make these accessible to other players via the Internet. This participative culture is placed in a historic framework by means of three case studies: LEGO toys, Sim City/The Sims and the citizen participation project Face Your World. The three case studies show how the more or less solitary 19th century game world is transforming into densely populated geographies. The place of the game literally (increasingly indoors) as well as metaphorically (players become producers). Although the participative culture is often regarded as the ultimate form of consumer emancipation, the fact remains that companies decide whether the boundaries between consumers and producers gradually disappear.

Key words:

Computer games, participative cultures

“Proteomics as a tool for biomarker detection; protein profiling in chronic and vascular disease”

“Advanced Thrombinoscopy”

Thrombosis is de second-largest cause of death and disease (stroke, embolism) in the Western world. However, clinicians still do not dispose of a universal test to determine the coagulability of blood.  In the last few years, it has been increasingly recognized that measuring the thrombin generation could fulfil this role. Therefore, various laboratories are searching for ways of determining the thrombin generation. This dissertation shows that the CAT technique (Calibrated Automated Thrombinoscopy) provides more information about the coagulation capacity of blood than all previous tests and that it also is the most accurate (automated) technique that is available at the moment. With this test, defects in the blood coagulation system as well as in the thrombocytes can be traced down and the treatment with for example heparins or oral anti-coagulation medication can be followed up and optimized.

“Challenging the Digital Imperative”

“Relationship between angiogenesis and the immune response against solid tumors”

A promising new anticancer strategy is inhibition of blood vessel formation (angiogenesis) in the tumour. This dissertation shows that tumours also protect themselves against the immune system via the process of angiogenesis. Substances that stimulate angiogenesis inhibit interactions between blood vessel wall and white blood cells, as a result of which the tumour escapes from immune cells that attack the tumour cells. This study confirms the hypothesis that inhibition of angiogenesis makes the tumour more vulnerable again to the immune system, so that the tumour is therefore fought at two fronts. Anti-angiogenesis reinforces the entry of white blood cells and consequently the immune response against the tumour. These results show that inhibition of angiogenesis will reinforce the effect of anti-tumour immune therapy. 

“Neurologic complications in small cell lung cancer”

Metastases to the nervous system are often the most common neurological complications of small cell lung cancer (SCLC). This research tries to give a more adequate description of numbers and to prevent neurological complications in general and brain metastases in particular. Moreover, a contribution is made to the debate about the changes in diagnostics for and the treatment of brain metastases in SCLC. This research shows among others that brain metastases are more often diagnosed thanks to the improvements of imaging techniques (MRI instead of CT), often already before the patient has complaints from these metastases. It turned out that brain metastases reacted less often to chemotherapy than the lung tumour and metastases elsewhere in the body. This dissertation also discusses the optimal treatment strategy for SCLC patients with brain metastases.

Key words:

lung cancer, nervous system, brain metastases

“Radiopaque Bioactive Microspheres as Injectable Biomaterials”

“The development of exhaled breath condensate; a noninvasive method of measuring airway inflammation"

This dissertation describes the development of a new method to simplify the diagnostics of airway inflammation, and to improve its treatment. In a completely painless and harmless way the exhaled breath of a toddler or child is collected and cooled down to drops of exhaled breath condensate. Subsequently, this fluid condensate is analysed for exhaled inflammation substances that can indicate the type and seriousness of an airway inflammation. This method makes it possible to, for example, measure the airway inflammation in asthma in a simple way, and to treat it more effectively. 

Key words:

Children’s lung diseases, airway inflammation

“The Institutional Politics of the European Union; An analysis of administrative governance and constitutional reform in the EU”

The dissertation of Thomas Christiansen studies a few important institutes of the European Union, particularly the way their development is influenced by the tensions and contradictions that are inherent to the making and implementation of European policy. On the basis of a theory that emphasizes the combined action of the political actors and structure characteristics of an organization, the PhD candidate presents the international politics as a process that goes via different dimensions. He applied this theory both to individual institutes, such as the European Commission and the Secretariat-General of the Council of the European Union (the ‘Council of Ministers), as to more general developments in European politics such as the reform of the European Treaty and the constitutional politics.

“Health technology assessment of organizational innovation in health care: the case of shared care in hearing aid provision”

The ageing of the population leads to an increased number of people with impaired hearing. That is one of the reasons why shared care is being developed for elderly people with a hearing impairment. In this shared care audiologists take over tasks from E.N.T. specialists and Audiological Centres  This dissertation evaluates if this improves the care. Both the professionals as the people with a hearing impairment appeared prepared to support shared care. Persons with a hearing impairment preferred a first visit to the audiologist, provided he/she is able to accurately recognize patients who need to be referred, and a hearing aid final check with the E.N.T. specialist. Shared care turned out less expensive than the current care, but less effective and not more efficient. Determining factors that deserve further research are the accuracy of the audiologist and an earlier call for help by the people with impaired hearing.

Key words:

health technology assessment; deafness; organizational innovation

“Explaining Success and Failure in Development.”​

“Tumor cell plasticity: vascularisation beyond angiogenesis”

The growth of tumours is to a great extent determined by the supply of oxygen and nutrients. Tumours sometimes secrete growth factors which stimulates the blood vessels around the tumour in growth; this is called angiogenesis. Besides the aptitude of regular blood vessels, in 1999 it was discovered that aggressive tumour cells are also capable of forming blood vessel type structures themselves, a process that is called vascular mimicry. These vessel structures are co-responsible for the aggressiveness of the tumour. So far, little is known about the role of this secondary circulation system in tumours. This dissertation studies the role of vascular mimicry in the biology of two aggressive tumours: skin melanomas and Ewing sarcomas. The findings make it possible to develop new therapies for aggressive tumours.

Key words:

tumour research, vascular mimicry

“Functionele neurochirurgie: een kwestie van elektrisch evenwicht” (‘Functional neurosurgery: a matter of electrical balance’)

“Breastfeeding and Infant Atopic Manifestations”

“Autobiographical memory retrieval; overgeneral memory and intrusions”

Autobiographical memories can be actively ‘sought’, but they can also suddenly recur in our heads without any effort. These memories play an important role in our identity, goals in life, and problem-solving. It is therefore not surprising that a disturbed retrieval pattern of autobiographical memories is related to psychological problems. This dissertation discusses the question why some people on the one hand find it difficult to consciously retrieve detailed autobiographic memories, whereas at the same time they have constantly recurring and very specific memories of major events in life. One of the reasons appears to be that in traumatized people the active search process seems to be disturbed, while the associative remembering is intact and that the retrieval of one autobiographical memory can cause forgetting the other.

Key words:

autobiographic memory, remembering

“On pediatric delirium in critical illness; a clinical multidisciplinary study in child neuropsychiatry at the PICU”

The delirium, from the Latin word ‘de-lira’ which means ‘disrupted’, is a serious neuropsychiatric disorder in critically ill adults and elderly people. It is related to longer hospitalization, a worse prognosis, and higher mortality, especially in combination with artificial respiration. Children in the home situation become delirious very quickly, especially as a consequence of an infection disease with fever and that has a very good prognosis. The PhD candidate investigated among others how often this phenomenon occurs in the Pediatric Intensive Care Unit of the azM (cumulative 5%, rising at a higher age), how the disorder manifests itself (the so-called presentation), how high the mortality is (12,5%) and how the reaction to medication appears to be (good). However, extensive follow-up research is necessary. 

“Leber’s Hereditary Optic Neuropathy: an interaction between two genomes ?”

“GSK-3B: central regulator of skeletal muscle plasticity”

Loss of muscular mass often occurs in chronic obstructive pulmonary diseases (COPD). Prevention and treatment of this muscular mass loss is increasingly recognized as an important pillar in the treatment of this chronic disease. For this purpose it is essential to understand the mechanisms of muscle degradation and muscle growth. The protein Insulin-Growth-Factor I (IGF-I) has an important role in muscle growth, but the way in which IGF-I is involved in muscle regeneration is still insufficiently clarified. This research shows that one of the signal ), has abproteins of IGF-I, Glycogen Synthase Kinase-3beta (GSK-3 central, inhibiting effect on muscle mass preservation, muscle  withbdifferentiation and regeneration. Targeted inhibition of GSK-3 the help of medication is possibly a promising treatment strategy to prevent loss of muscular mass and to stimulate muscle growth in COPD and other chronic disorders.  
This research was financed by the ‘Nederlands Astma Fonds’ (NAF).

Key words:

COPD, skeletal muscle weakness, treatment strategy

“Managing concerns about falls; Fear of falling and avoidance of activity in older people”

“Implications of cardiac troponin T degradation”

Troponins are proteins that are involved in muscle contraction. They can be found in all muscle cells. In the case of muscle damage these proteins end up in the circulation. The heart is a muscle with troponins that only occur there, the heart-specific troponins. By means of sensitive diagnostic tests these can be measured in the blood to diagnose a heart infarct. This research shows that the troponins in the blood circulation disintegrate. That is why it is not possible to determine for certain what is exactly measured. This has consequences for the comparison of different tests and it can complicate the diagnosis of a heart infarct on the basis of this test.

Key words:

Hartinfarct, Troponine T

“The lipolytic Pathway in the Obese Insulin Resistant State”

Obesity is one of the main health problems of this century. An increased storage of fats in the fatty tissue and the skeletal muscle is an important symptom of obesity and  type 2 diabetes mellitus (geriatric diabetes). This dissertation shows that people with obesity have a reduced ability of mobilising fats from the fatty tissue and the skeletal muscle (lipolysis). Both our genes as environmental factors seem to play an important role here. More insight in the underlying mechanisms for the disturbed lipolysis can lead to the development of new medicines and lifestyle interventions for the prevention of treatment of obesity and geriatric diabetes.

​Key words:

obesity, fatty tissue, skeletal muscle

“Refractive errors: occurrence, aspecific health complaints, and functional problems”