Academic Ceremonies April 2012

“Treewidth; structural properties and algorithmic insights”

“Coping with mutant ubiquitin in health and neurodegenerative disease”

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

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

Key words:

multimorbidity, general practice, health effects

“Peri- and extravascular inflammation: impact on Atherosclerosis”

“On the Economic and Strategic Implications of Science”

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

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

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

Key words:

smoking cessation treatments, genetic differences, genetic test

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

“Epicardial amiodarone therapy for atrial fibrillation”

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

Key words:

atrial fibrillation, amiodaron, local application, hydrogel, patch

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

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

“Bargaining and Judgment Aggregation”

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

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

Key words:

arrhythmias, electrophysiology, computer models, systems-biology

“Staphylococcus aureus biofilm”

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

Key words:

Staphylococcus aureus bacterium, biofilm, coating

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

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

Key words:

metabool syndroom, vetopslag, skeletspier, insulinegevoeligheid

“Models in official statistics”