Academic Ceremonies December 2009

“The regulation of protein synthesis by mTOR signaling: a potential target for cancer treatment?”

During the development of cancer, the activity of the protein kinase mTOR is often elevated, leading to increased proliferation and survival of tumor cells. It is thought that mTOR does this by influencing protein synthesis. This thesis describes how mTOR inhibits protein synthesis under reduced oxygen levels (hypoxia), a common feature of solid tumors. Furthermore, the results show that blocking mTOR activity with a drug called rapamycin slows tumor growth, but that it also increases the amount of hypoxic tumor tissue, an undesirable effect that can make tumors more aggressive and resistant to conventional therapy.

Key words:

cancer, mTOR, hypoxia, rapamycin

“Respiratory tract infections in general practice – enhanced communication skills and C-reactive protein testing to optimize management”

Many Dutchmen visit their general practitioner each year with serious complaints about coughing that can restrict their daily occupations. Usually, antibiotics don’t work in the case of coughing complaints that are caused by respiratory tract infections. But still, they are often prescribed and used. This dissertation studied the treatment methods for 659 patients of 70 general practitioners with a view to make the antibiotics use for coughing complaints more adequate. When general practitioners used a short-term test to exclude serious infections (the so-called C-reactive protein test on one single drop of blood) or gave their patients the necessary explanation after training in communication skills, they prescribed considerably fewer antibiotics, while the patients recovered just as quickly. (Funding: ZonMW).

Key words:

respiratory tract infections, cough, antibiotics, general practice, common complaints

“The realities of life for people with severe and profound intellectual disabilities and mental health problems”

“The role of haptoglobin phenotype and 24-hour blood pressure characteristics in cerebral small vessel disease”

“Exercise training in cancer survivors”

At the end of the nineties, rest was regarded the best approach for patients who recovered from treatment after cancer. In her dissertation, however, Ingrid De Backer shows that in fact an intensive training programme strongly improves the physical condition and quality of life of these patients. Such training programmes should be individually oriented by means of reliable and valid effort tests. A highly intensive power and interval training turns out possible for almost all patients provided they receive good support. The result is a substantial improvement of muscular strength, condition, fatigue and quality of life. These positive effects remain up to a year after the end of the training programme. Compared to a patient group that received no training there was a difference in muscular strength of approximately 65 % about 18 months after treatment.  Finally a considerable part (20%) of quality life of cancer patients can be explained by physical variables among which muscular strength and permanent shape.

“WIRED for learning. How computers can support interaction in small Group learning in higher education”

“The Tension between Rules Regulating the (Liberal) Professions and EC Competition Law – Reason and Passion in discussing professional regulation in EC competition law”

This dissertation studies the classic liberal professions, i.e. the legal, medical, technical and accountancy professions. In spite of the fact that the modus operandi of the free professions limits the access and practice of them, these professions are traditionally regarded to be in the general interest because – besides their economic interest – they assume a public role.  This dissertation examines the public interest of having an effective system for, for example, health care and administration of justice, and relates it to the European Competition Law with its guarantees for the functioning of the rule of law.

“Knowledge, Learning, and Teaching: Studies on the application of constructivist principles in higher education”

“The interstitial cells of the urinary bladder”

“Why stress causes psychosis and psychosis causes stress”

Stress plays an important role in the development of a psychosis. This dissertation studies the underlying mechanisms of this stress sensitivity. It turns out that trauma in childhood leads to greater stress sensitivity in adulthood, which in turn is a risk for the development of psychosis. People with sensitivity to psychosis also appear to show deviations in the stress hormone cortisol. Moreover, psychotic symptoms themselves also cause stress with which patients sometimes find it difficult to cope. Bases on these results it appears important to attune the treatment of psychosis more to this underlying stress sensitivity. 

Key words:

psychose, stress, stressgevoeligheid, trauma, cortisol, coping

“Evaluation of the Primary Mouse Hepatocyte Model for the Prediction of Genotoxicity”

“New approaches for immune modulation in Myasthenia Gravis”

“Biomechanical Analysis for Abodominal Aortic Aneurysm Risk Stratification”

The aorta is the biggest coronary artery in the body. Infections and weakening of the aorta wall can cause a widening in the aorta, a so-called aneurysm. Aneurysms occur the most often in the abdominal aorta in the navel area (then it is called an AAA). About 4% of the men over 55 years old have an AAA, and 1% of the women. AAA’s become increasingly wide and the risk of aorta wall rupture increases. Whether the wall will rupture not only depends on the maximum diameter, as is assumed in current diagnoses. A better risk prediction can be made by calculating the wall tension. In this dissertation these calculations were optimized and standardized for future diagnoses.

“Quality of life and criminal recidivism in forensic outpatients with personality disorders. A good live approach”

In the treatment of patients with a personality disorder who committed an offence the emphasis is on reducing the risk of offence repetition. Until recently, there was hardly any attention for risk factors that can have a protective effect. This dissertation focuses on the possibly protective effect of certain factors, namely the life conditions of the patient and the degree of satisfaction about these conditions, outlined in the concept quality of life. The results show that participation in social institutions, and particularly organized recreation, can have a protective effect. Moreover it turned out that satisfaction with various domains and general satisfaction, as well as the way a person feels in life, can be protective for criminal behaviour. Quality of life is a subject that deserves attention in the treatment of forensic patients, with a view to reduce the risk of offence repetition.

Key words:

forensic psychiatry, quality of life, protective factors

“Use of tacrolimus in Chinese renal transplant recipients”

“Dietary Determinants of Obesity”

In this thesis we investigated the associations of dietary glycemic index (GI), glycemic load (GL), energy density (ED) and fiber intake with change of body weight and waist circumference, using data from a large cohort study with participants from five European countries. We found a beneficial effect of low GI, high fiber, low ED diet in the prevention of weight and waist gain, in spite of the small effect sizes. In addition, a significant interaction between dietary GI and a genetic variant was observed. Our results suggest that it may be appropriate to recommend a low ED, high fiber and low GI diet for the prevention of (abdominal) obesity

Key words:

obesity, diet, glycemic index, glycemic load, energy density

“Mechanisms of Vasidilation in early pregnancy. Studies in instrumented consciousrats and isolated rat arteries”.

“A molecular basis for the loss of muscle oxidative phenotype: Implications for COPD”

Chronic obstructive pulmonary disease (COPD), associated with smoking behaviour of years, is characterized, not only by a loss of lung function, but also by deviations in the metabolism of the leg muscles which causes the muscles to acidify more quickly. Because of this, the patients tires quickly and he is restricted in his daily functioning. This dissertation shows that important regulators of muscle metabolism are less present in the leg muscles of COPD patients. This reduction of the protein content is inversely related to the quantity of inflammatory substances in the blood. Moreover, we show that the inflammations in the muscle can be directly involved in deviations in the muscle metabolism. This opens new perspectives for the use of anti-inflammatory substances in the treatment of these deviations.

Key words:

COPD, spiermetabolisme, ontsteking

“Toddling ‘long the River Meuse. Integrated Assessment and participatory Agent Based Modelling to support River Management”

“Role of Neutrophils in Pulmonary DNA damage and repair”

Chronic pneumonia is an important risk factor for the development of pulmonary cancer. This dissertation studied the infiltration of neutrophils in the bronchial tubes as a possible cancer enhancing mechanism of inflammation. Neutrophils form an important source of oxygen radicals (RZS) in the inflamed lung. The release of these RZS increases the damage to the genetic material (DNA) in the lung and obstructs its recovery. The inhibition of the DNA recovery can anchor the DNA damage and thus initiate cancer. Of course, these findings are also important for other organs in which the development of cancer can be associated with a previously existing inflammation.

Key words:

pulmonary cancer, neutrophils, oxygen radicals, DNA

“Monotonicity and Bayes-Nash Implementation”

“A wavelet approach to cardiac signal processing for low-power hardware applications”

The number of deaths caused by hearth diseases has been reduced among others by implantable applications such as pacemakers. The better we can inform the pacemaker about what goes on in the heart, the better it can do its job. By using so-called wavelets measured heart signals are reproduced differently so that they can be filtered and show specific characteristics of the heart, for example the heartbeat. The dissertation describes a design procedure for wavelets, linked to a specific task. It also describes how these wavelets can be incorporated in analogue chips, as a result of which they use little power and are suitable for use in implantable applications.

Key words:

heart, signal processing, analogue, wavelet, wavelet design, ECG, L2 approach

“Cerebral microembolic signals in cardiac interventions”

The quantity of microembolisms in the brain is an indication of possible neurologic complications. A comparison in the number of cerebral microembolisms shows that in a minimal invasive surgical intervention for cardiac arrhythmias (pulmonary vein ablation -PVI) there is less risk of postoperative neurologic complications than in the standard cardiologic therapy. In the cardiologic therapy, where a catheter is brought into the heart, the quantity of cerebral microembolisms depends on the type of catheter. During open-heart surgery the formation of microembolisms is inevitable. A new technology can prevent that they end up in the brain vessels. By placing an ultrasound transducer on the aorta during open-heart surgery, microembolisms can be deflected under the emission of ultrasound in the direction of the aorta descendens.

Key words:

cerebral microembolisms, cardiac arrhythmias, neurological complications

“Hormone-induced changes in the coagulation system”

The hormonal changes during pregnancy and contraceptive use are risk factors for venous thrombosis. In this thesis the effects of oral contraceptives on coagulation were compared with that of hormonal contraceptives with alternative (transdermal, vaginal, intrauterine) routes of administration. Furthermore, we studied the underlying mechanisms of the hormone-induced prothrombotic changes in a mouse model. The results of the studies indicate that the hormone-induced risk of venous thrombosis can at least partially be explained by a decrease of the plasma levels of natural anticoagulants, i.e. tissue factor pathway inhibitor and protein S. A better understanding of the hormone-induced changes in coagulation may help to reduce the incidence of thrombosis during hormonal contraception or pregnancy.

Key words:

hormonal contraception, venous thrombosis, coagulation system

“VEGFR-1 function and dysfunction in monocytes”

Monocytes are white blood cells that are involved in wound healing and the growth of blood vessels. Monocytes migrate to the location where new blood vessels are formed because they are drawn by the growth factors VEGF-A and PIGF (via stimulation of VEGF receptor-1). This ‘chemotactic’ response is weakened in diabetes patients. This dissertation studied the monocyte migration at the molecular level and investigated how this process is disturbed in diabetics. This research found indications that the weakened chemotactic response is caused by an increased RAGE expression and increased oxidative stress, leading to desenzitation of the VEGRF-1 responses. These findings can be regarded as a new molecular concept for diabetes-related cellular dysfunction.

Trefwoorden:

monocyten, diabetes

“Gait and balance characteristics in patients with diabetes type 2. Evalaution and treatment efficacy”

The World Health Organization has described type 2 diabetes as an international epidemic. This PhD project showed that the gait capacity of diabetic individuals decreases and fall risk increases at an early stage of the disease. In addition the effect of a specific training (physiotherapeutic group training including gait and balance exercises with function-orientated strengthening) on patients’ gait and balance was tested. The specific training could improve diabetic patients’ gait speed and balance and increase muscle strength and joint mobility. Further studies are needed to explore these improvements’ influence on the number of reported falls, patients’ physical activity level and quality of life.

“Epidemiological studies into prodromes and risk factors for cognitive decline and dementia”

“Doing Artworks”

During the last three decades, installation artworks have become mainstream in contemporary artistic practices. Acquiring and displaying such works, however, implies that curators and conservators have to deal with obsolete technologies, ephemeral materials and other problems concerning the care and management of these artworks. Installation artworks challenge traditional museum practices of collecting and conservation. How do museums approach these challenges and how to understand the role of conservation theory and ethics in these practices? Drawing on fieldwork in contemporary art museums, this thesis explores how key concepts such as authenticity and artist’s intention figure in day-to-day museum work. Moreover, the study shows how conservation practices behind-the-scenes play an important role in the perpetuation of installation artworks. Consequently, it argues that the common distinction between front (presentation and display) and back (conservation and collection management) is particularly untenable in the case of installation artworks. 

Key words:

contemporary art, conservation and restoration, museums, cultural heritage

“Lumbar extensor training in low back pain management”

“A dynamic Model of the Qnset of Clinical Psychosis from an Epidemiological Perspective”

Although psychosis has been commonly considered a rare phenomenon outside the range of normal human experience, psychotic experiences have been shown to be expressed at levels well below its clinical manifestation. This thesis examines how the psychosis phenotype exists in nature and investigates the dynamic process driving psychosis expression from mental wellness to onset of clinical psychosis within the general population. Ten percent of the general population have attenuated psychotic experiences which are mostly transitory. When influenced by stress-related environmental risk factors these experiences become abnormally persistent, with an increasing risk of becoming clinically relevant over time. Both the individual’s developmental liability and the context of affective deregulation play a roll driving psychosis expression to the onset of clinical psychosis.

Key words:

psychosis, emotional disadjustment, adolescents

“Modulation and Adaption in the Normal and Obstructed Urinary Bladder”

Patients with an Overactive Bladder (OAB) syndrome suffer from uncontrollable urge to urinate, incontinence and frequent urinating. In the Netherlands 12% of the people suffer from the OAB syndrome. It occurs among others in men with an enlarged prostate. This dissertation discusses bladder disorders as a consequence of a narrowing of the guinea-pig urethra, a simulation model for prostate enlargement. Our hypothesis is that an increased bladder muscle activity stimulates sensory nerves in the bladder wall which can cause urinary complaints. Particularly investigated was the role that interstitial cells, prostaglandins and oxidative stress play here. A better understanding of changes in the bladder wall contributes to more effective treatment methods for patients with overactive urinary complaints.

Key words:

bladder, obstruction, urinary incontinence.

“Embryological and surgical aspects of the tethered cord”

In a tethered cord, the spinal marrow because of a development disorder, that is always part of the spina bifida spectrum, fixed at a certain point in the vertebra channel. In many cases this leads to neurological failure. This dissertation describes the neurosurgical treatment of several rare innate disorders of the central nervous system, associated with a tethered cord. The emphasis is on the embryological origin, the clinical and radiological diagnostics and the neurosurgical treatment. The new insights into the embryological development and detailed descriptions of the surgical anatomy are guidelines for the treatment of patients with these rare disorders. Some of these new insights were recently incorporated in an international study book on paediatric neurosurgery.

Key words:

spina bifida, tethered cord, neurosurgery, embryology

“On Regional Differences in Sick Leave. The role of work, individual and health characteristics and socio-cultural environment”

This dissertation concludes that – besides sickness or type of work – region-bound socio-cultural factors influence sick leave. For reducing sick leave in certain regions on the national level, regional socio-cultural differences must be taken into account, because they can cause a different effect from sick leave determinants per region that are known in the literature. In this research that is, for example, the sick leave determinant autonomy on the work floor. Among others (inter)nationally operating companies and safety, health and welfare services have to be aware of that. The propositions with the dissertation among others discuss the lack of a legal regulation for the assessment of applications in the domain ‘care and wellbeing’ (AWBZ and Wmo), which puts the implementation quality of these laws under pressure. 

Key words:

sick leave, region-bound

“More bang for your Buck. The effects of consumer experience, multiple brand association types, and brand alliance form on the perceived value of education”