Epileptic seizures are associated with changes in autonomic function. Ictal asystole, when it leads to syncope, can cause severe traumatic falls. We discovered a new indirect method, based on video... Show moreEpileptic seizures are associated with changes in autonomic function. Ictal asystole, when it leads to syncope, can cause severe traumatic falls. We discovered a new indirect method, based on video, EEG and ECG, to disentangle if vasodilatation was the dominant mechanism behind the syncope. In this group of patients, pacemaker implantation is less helpful. Autonomic manifestations of epilepsy can also help to detect seizures. Our literature review discovered that combining different modalities in one detection device provides higher sensitivity, and personalization of detection algorithms can decrease false alarm rate. We validated a wearable multimodal detection system (NightWatch) on children at home. NightWatch showed high sensitivity for the detection of potentially dangerous nocturnal seizures, reduces caregiver stress and saved costs from a societal perspective. Validation of an automated video detection system showed that this could provide a good alternative for children who cannot tolerate a wearable device.From different qualitative user studies, we concluded that caregivers’ needs for seizure detection vary greatly. Also, the success of device implementation is highly dependent on the protective behavior parents developed towards their child with epilepsy. This emphasizes the importance of tailored and user-centered approaches for seizure detection. Show less
In a social environment composed mostly of people with typical hearing, deaf or hard of hearing (DHH) children experience social interactions differently from their typically hearing (TH) peers,... Show moreIn a social environment composed mostly of people with typical hearing, deaf or hard of hearing (DHH) children experience social interactions differently from their typically hearing (TH) peers, which could guide them towards different patterns for processing other people’s emotions. This thesis aimed to unravel whether hearing status affects how children encode, interpret, and react to others’ emotions in a social context, and whether their responses are associated with psychosocial functioning, using a variety of measures that included eye tracking, pupillometry, behavioral tasks, parent reports, and longitudinal follow-up. DHH children’s skills for perceiving others’ basic emotions were on par with their TH peers. Improved emotional functioning was associated with improved psychosocial functioning to a similar degree in DHH and TH children alike. Yet, DHH children still faced difficulties when they had to process an emotion with adequate knowledge about social rules and causes of emotions. Moreover, DHH children used a visual cue-based encoding strategy to compensate for ambiguous or unavailable information in social situations, and recruited more cognitive resources to process unfamiliar emotional expressions. The findings underscore the need to look into possible qualitative differences between typical and atypical development. These individual differences reflect compensatory strategies to support daily living, or signal a need for support in a certain domain. Show less
Childhood obesity is an increasing health issue. In the first part of this thesis comorbidities in children with obesity were studied, concerning the diagnostic process and dosing regimens. In... Show moreChildhood obesity is an increasing health issue. In the first part of this thesis comorbidities in children with obesity were studied, concerning the diagnostic process and dosing regimens. In children with obesity and respiratory symptoms the diagnosis of asthma was studied and in children with ADHD dosing regimens. Overtreatment as a consequence of overdiagnosis was frequently observed in children with obesity and asthma and undertreatment due to relative underdosing in the ADHD population with obesity. This highlights the necessity for accurate diagnostic processes alongside dosing regimens based on pharmacokinetic changes caused by obesity. The focus in the second part of this thesis was on screening for complications of obesity namely insulin resistance and cardiovascular diseases. Given the high prevalence of insulin resistance and the observed changes of cardiovascular parameters, screening on cardiometabolic complications is warranted in all children with obesity. Pharmacological treatment with metformin in addition to lifestyle intervention was studied in the last part of this thesis. Given the favorable effect on BMI in children and adults and the maintenance of weight loss and reduction in progression towards T2DM in adults, metformin can be considered in children with obesity and insulin resistance in addition to lifestyle intervention. Show less
De overheid mag kinderen onder voorwaarden van hun vrijheid beroven met als doel ze op te voeden en te beschermen. In de Nederlandse context wordt deze vorm van vrijheidsberoving ‘gesloten... Show moreDe overheid mag kinderen onder voorwaarden van hun vrijheid beroven met als doel ze op te voeden en te beschermen. In de Nederlandse context wordt deze vorm van vrijheidsberoving ‘gesloten jeugdhulp’ genoemd, geregeld in de Jeugdwet. Met dit onderzoek is beoogd om een kinder- en mensenrechtentoetsingskader op te stellen, waaraan de Nederlandse wet en de toepassing getoetst wordt. Tevens biedt het onderzoek inzicht in 200 jaar historie.Verder zijn 586 rechterlijke uitspraken over een periode van 10 jaar (2008-2017) geanalyseerd. Hieruit blijkt dat een plaatsing vaak gebaseerd is op het inzetten van acute hulp in een situatie waar in niets anders mogelijk lijkt te zijn. Doorgaans wordt daarbij onvoldoende gekeken naar het doel van deze plaatsing en de vrijheidsbeperkingen die dit met zich meebrengt.In dit onderzoek komen ten slotte 23 kinderen aan het woord die te maken kregen met een gesloten uithuisplaatsing. Uit het onderzoek blijkt dat de legitimiteit van het op grote schaal toepassen van deze maatregel onder druk staat, met name omdat het nogal eens ontbreekt aan passende zorg. Verschillende aanbevelingen worden gedaan om de legitimiteit te verbeteren, onder meer door middel van verdieping van het juridische toetsingskader, verkorting van de maximale duur van een plaatsing. Show less
International Commercial Surrogacy (ICS) has emerged over the past decade as a modern method of family formation. ICS is unregulated internationally and domestic laws are struggling to keep pace... Show moreInternational Commercial Surrogacy (ICS) has emerged over the past decade as a modern method of family formation. ICS is unregulated internationally and domestic laws are struggling to keep pace with ICS. However, a child is at the centre of every ICS arrangement, and children conceived and born through ICS are at a heightened risk of their rights being infringed.Written over the course of time when ICS has rapidly developed, this book explores why and how the child's rights are at risk in ICS, and seeks to apply the standards and norms of the United Nations Convention on the Rights of the Child to the ICS context. This book proposes approaches for balancing the competing rights and interests of the child and other parties in ICS. It presents a framework for protecting the rights of children born through ICS, illustrating that this is achievable in practice, in the absence of international consensus on ICS as a phenomenon.This book is relevant for child rights practitioners and academics, and useful for policy-makers, legislators and national and international decision-makers grappling with the children’s and human rights issues presented by this 21st century human rights challenge. Show less
The aim of this thesis was to study the link between hearing loss, language skills, and social functioning in deaf and hard of hearing (DHH) children. Sufficient language skills are an... Show moreThe aim of this thesis was to study the link between hearing loss, language skills, and social functioning in deaf and hard of hearing (DHH) children. Sufficient language skills are an essential prerequisite to develop appropriate communication skills, in order to join in conversations with others. Both their hearing loss and their diminished communication skills prevent DHH children from learning by observing their surroundings (incidental learning). As a result, DHH children showed more difficulty in understanding others’ thoughts and wishes (Theory of Mind or ToM). DHH teenagers reported to have difficulties with understanding others’ emotions and showed lower levels of prosocial behavior. Higher communication skills, but not language skills, were related to better ToM development and higher empathic abilities. Second, the role of early identification and intervention of hearing loss on the social-emotional development of DHH children was studied. This was illustrated in a longitudinal study showing that early cochlear implantation resulted in higher language and communication skills. In turn, these improved skills prevented the development of early signs of psychopathology. To conclude, this thesis shows that in order to stimulate the social-emotional development of DHH children, their opportunities for incidental learning have to be increased. Show less
In haar proefschrift heeft Katinka Beker onderzoek gedaan naar de fundamentele leesprocessen die ten grondslag liggen aan leren van (meerdere) teksten. Uit een combinatie van literatuur- en... Show moreIn haar proefschrift heeft Katinka Beker onderzoek gedaan naar de fundamentele leesprocessen die ten grondslag liggen aan leren van (meerdere) teksten. Uit een combinatie van literatuur- en experimenteel onderzoek is gebleken dat het activeren van eerder gelezen informatie en achtergrondkennis tijdens het lezen belangrijk is bij het leren van teksten. Door een nieuw onderzoeksparadigma te gebruiken kon op een subtiele manier onderzocht worden of informatie uit eerder gelezen teksten of achtergrondkennis actief was tijdens het lezen van nieuwe teksten. Het paradigma kan in toekomstig onderzoek gebruikt worden om te onderzoeken onder welke omstandigheden informatie uit eerder gelezen teksten of achtergrondkennis geactiveerd wordt tijdens het lezen van nieuwe teksten. Het onderzoek is vooral fundamenteel van aard, maar bevat ook een aantal aanknopingspunten waarmee in toekomstig praktijkgericht onderzoek mogelijk een vertaalslag gemaakt kan worden voor de onderwijspraktijk. Zo lijken consolidatie- en verrijkingsprocessen belangrijk te zijn bij het leren van teksten. Show less
Coeliac disease (CD) is an immune-mediated systemic disorder elicited by gluten in genetically susceptible individuals. The aim of this thesis was to investigate the influence of infant feeding on... Show moreCoeliac disease (CD) is an immune-mediated systemic disorder elicited by gluten in genetically susceptible individuals. The aim of this thesis was to investigate the influence of infant feeding on prevention and development of childhood CD (part 1) and to explore new strategies for improvement of care for CD children and young adults (part 2). In part 1, the European multi-centre randomized double-blind placebo-controlled dietary intervention-study in high-risk children (www.preventcd.com) is presented. Based on retrospective studies suggesting a ‘window of opportunity’ for primary prevention of CD, parents were advised to introduce gluten between 4–6 months of age. Our results show that this did not reduce the risk of CD by 3 years of age and contributed to a new European guideline stating that gluten may be introduced between age 4-12 months. Part 2 shows that physicians overestimate the CD specific health-related quality-of-life (HRQOL) of CD patients, supporting implementation of self-reported CD-specific HRQOL measurements during follow-up. Compared to traditional hospital visits for treated CD, E-health was cost-saving, satisfactory, and significantly improved the CD-specific HRQOL. As E-health requires a point-of-care test suitable for follow-up of treated CD, three different tests were compared with conventional ELISA and one was found to be suitable. Show less
Increasingly, pleas are made for extending the involvement of minors in decision-making about participation in pediatric research. However, a number of issues arise from this desired... Show more Increasingly, pleas are made for extending the involvement of minors in decision-making about participation in pediatric research. However, a number of issues arise from this desired participation of minors. First, involvement in decision-making requires children and adolescents to be adequately informed about what participation in research entails. Second, the plea for increased involvement in decision-making requires further investigation whether children indeed can, should and want to play a role in the decision about research participation. This thesis addresses these issues and thereby contributes to insights in how to empower minors in the context of informed consent for research participation. New informed consent material was developed in close cooperation with children and other end-users, the process of which is described and evaluated. Also, insights in the role that minors can, should and want to play in the informed consent procedure are described. These insights were obtained by reviewing multidisciplinary scientific evidence on the competence of minors, by an ethical reflection on the view on children that we should adopt, and by consulting minors themselves about the perspectives on their role in decision-making. Finally, based on this research, recommendations are provided on how to empower minors in decision-making about research participation. Show less
When trying to understand texts, readers engage in various cognitive processes. If all goes well, the engagement in these cognitive processes during reading results in the construction of a... Show moreWhen trying to understand texts, readers engage in various cognitive processes. If all goes well, the engagement in these cognitive processes during reading results in the construction of a coherent mental representation of the text, the essence of successful reading comprehension. To construct such a representation, readers need to monitor the coherence of the text and of their emerging mental representation of what the text is about. The central aim of the empirical studies described is to examine coherence-monitoring processes across development by measuring reader’s ability to detect coherence breaks during reading of narratives. The first part of this dissertation consists of three empirical studies (chapter 2-4). The first study examined whether good and poor comprehenders at age 8-9 and 10-11 detected coherence-breaks during and/or after reading. The second study builds on the first study by examining the protracted development of coherence monitoring in an adolescent population (ages 10-22) using the same task under more challenging circumstances. The third study explored the neural correlates of coherence-break detection in young adults in an fMRI study. The second part of this dissertation consists of two conceptual chapters in which the results are summarized and discussed in a broader theoretical perspective (chapter 5-6). Show less
Special populations are groups of patients that may respond differently to drug treatment due to a variety of factors, such as age or disease. Therefore, in drug development dedicated clinical... Show moreSpecial populations are groups of patients that may respond differently to drug treatment due to a variety of factors, such as age or disease. Therefore, in drug development dedicated clinical studies are often required to determine the optimal dose for these (vulnerable) patient groups. Such studies are complicated by ethical and practical barriers that can hinder the objective of the study when not well designed. To optimise the design of such studies, the application of model-based approaches is essential. In this thesis, we aimed to develop a semi-physiological framework that constitutes a scientific basis for optimisation of study designs in special populations. First, we examined the accuracy of existing approaches in paediatric patients. For the "allometric scaling plus maturation function" approach, the accuracy was shown low especially in young children. An alternative approach was found in the physiological well-stirred-model of hepatic clearance. On this basis, the semi-physiological PK models were developed by interfacing descriptive compartmental pharmacokinetic models with the well-stirred-model of hepatic clearance, and a mechanistic description of plasma-protein binding. The performance of these models was evaluated using two paradigm-drugs (solifenacin and tamsulosin) and was shown successful for the prediction of the pharmacokinetics in paediatric, hepatic-impaired and renal-impaired patients. Show less
This thesis describes the potential role of non-invasive measurement of pharmacokinetics (pk) and pharmacodynamics (pd) in the research and development of central nervous system (cns) stimulants or... Show moreThis thesis describes the potential role of non-invasive measurement of pharmacokinetics (pk) and pharmacodynamics (pd) in the research and development of central nervous system (cns) stimulants or depressants for children and adolescents. First, we evaluated the feasibility of using saliva as an alternative to plasma in two studies on psychostimulants (caffeine and methylphenidate). Second, neuropsychological and neurophysiological functions were measured longitudinally using the NeuroCart, a battery of tests developed at the Centre for Human Drug Research (chdr, Leiden, The Netherlands) that includes non-invasive tests for alertness, visuomotor coordination, motor control, memory, and subjective drug effects. Using a non-invasive approach, age-dependent differences in alcohol pk and pd were evaluated between healthy adolescents and adults. This thesis concludes with the report of two clinical trials that were designed to evaluate age-appropriate formulations of sedative drugs that have the potential for use in children. Show less
Large numbers of children all over the world face significant health risks, such as infectious and chronic diseases, malnutrition, injuries and the consequences of natural disasters, protracted... Show moreLarge numbers of children all over the world face significant health risks, such as infectious and chronic diseases, malnutrition, injuries and the consequences of natural disasters, protracted armed conflicts and poverty. Every year, 4 million babies die within the first month of their life and almost 8 million children under the age of five die from preventable diseases such as malaria, pneumonia, measles and diarrhoea. These general statistics do not reveal the underlying inequalities in health between and within countries. One of the causes of the inequalities is that, in many countries, vulnerable groups of children have no or only limited access to health services. This research aims to identify the standards in international law for realizing the right to the highest attainable standard of health of the child. The central questions that are analysed: a. What priorities derive from the concept of the highest attainable standard of health of the child, its definition and the interpretation of the key constituent elements on the basis of international human rights law? b. How should this concept be implemented in the light of the international human rights standards? Show less
This descriptive and analytical study is based on two corpora of audiovisual data of monolingual and multilingual children’s babbling and first words gathered in Mali during a period of nearly a... Show moreThis descriptive and analytical study is based on two corpora of audiovisual data of monolingual and multilingual children’s babbling and first words gathered in Mali during a period of nearly a year. It is concerned with fundamental discussions about the development and acquisition of language such as the issue of the presence or absence of evidence of early specialization in children at the babbling stage, the continuity between babbling and first words, and the emergence and development of phonology in children Show less
This research offers a comprehensive analysis of the International Criminal Court (ICC) and its core legal texts from a children’s rights perspective. It examines the ICC provisions and its case... Show moreThis research offers a comprehensive analysis of the International Criminal Court (ICC) and its core legal texts from a children’s rights perspective. It examines the ICC provisions and its case law, evaluating whether these meet international children’s rights standards, particularly as regards the protection of child victims and witnesses, their participation as victims in ICC proceedings and their role as beneficiaries in reparations. The manuscript proposes recommendations that could be adopted in order to guarantee children’s rights in ICC proceedings. The research is a useful tool for practitioners as well as for academics, both in the area of international criminal law as well as children’s rights. Show less
Many skin diseases among schoolchildren in sub-Sahara Africa cause disturbing complaints like itch and pain and several of them are contagious.This high prevalence causes a major public health... Show moreMany skin diseases among schoolchildren in sub-Sahara Africa cause disturbing complaints like itch and pain and several of them are contagious.This high prevalence causes a major public health problem.Although in several countries and also in our studies skin diseases present in large numbers, they don't get the attention they deserve.A high percentage of visits to hospitals or other health institutions are caused by skin diseases.Most of them can easily be prevented and treated. The majority of skin diseases found in our study was caused by infections and inflammation together and can be grouped into fewer than eight categories. This is important in designing training programs for medical teams involved in the delivery of health care services in sub-Sahara African countries where a big part of the population is less than 15 years of age. Show less
In this dissertation we present the results of our research on Helicobacter pylori infections in childhood, focusing on the prevalence, diagnosis and treatment of the infection. Our studies were... Show moreIn this dissertation we present the results of our research on Helicobacter pylori infections in childhood, focusing on the prevalence, diagnosis and treatment of the infection. Our studies were conducted in the Netherlands, Europe and Indonesia. We discuss diagnostic tests, therapeutic regimens, resistance and preventive measurements. We highlight clinical and pathophysiological aspects of the infection and describe which particular strains are prevalent and how transmission occurs. Presently, there are no established correlations between a Helicobacter pylori infection and recurrent abdominal pain, gastroesophageal reflux disease or growth retardation. We present data on the prevalence of Helicobacter pylori in young infants in the Netherlands and observe that children with at least one non-Dutch parent form a risk group. We assess risk factors in a Europe-wide study on gastroduodenal erosions and ulcers in childhood. In our study, Helicobacter pylori infection and gastrotoxic medications were relatively little implicated as etiology of that pathology. The prevalence of Helicobacter pylori infection in Indonesian young children is relatively high and points at an early acquisition of the infection. Finally, the resistance of Helicobacter pylori to clarithromycin and metronidazole was assessed for adults and children in the Netherlands. Low resistance rates were found, but the resistance in adults is increasing. We conclude that a test-and-treat regimen is justified for the Netherlands. Show less
Improving survival rates in children and adolescents with malignant bone tumours, paved the way to the application of new surgical extremity-salvage techniques. For the surgical treatment of... Show moreImproving survival rates in children and adolescents with malignant bone tumours, paved the way to the application of new surgical extremity-salvage techniques. For the surgical treatment of malignant bone tumours of the lower extremity, there are a number of resection options (amputation, limb sparing, and rotationplasty) available. Each option has its own indication and after the surgery different advantages and disadvantages. The debate is whether limb-salvage or ablative surgery is advantageous for the individual patient. Purpose of the studies presented in this thesis are evaluate and compare QoL, functional ability and physical activity levels among children and young adults in the first years after bone cancer surgery of the leg. A cross sectional and a prospective study were conducted in the Dutch university bone cancer centres. The results of the cross-sectional study show that outcomes are equivalent for those undergoing limb salvage or ablative surgery. The results of the prospective study showed that; survivors improve in the two years following resection of the bone tumour and the resulting limb-sparing or ablative surgery at all domains evaluated, with the exception of the mental QoL domains. These improvements were most pronounced over the first year after surgery. Show less
In mijn proefschrift richt ik mij op het probleem dat medisch-ethische toetsingcommissies onder de huidige Wet Medisch-wetenschappelijk Onderzoek met mensen soms onderzoeksvoorstellen moeten... Show moreIn mijn proefschrift richt ik mij op het probleem dat medisch-ethische toetsingcommissies onder de huidige Wet Medisch-wetenschappelijk Onderzoek met mensen soms onderzoeksvoorstellen moeten afkeuren die de zorg voor toekomstige zieke kinderen zouden kunnen verbeteren. In deze wet staat namelijk dat de risico__s en belasting van studies die de deelnemende kinderen niet direct ten goede kunnen komen, nooit meer dan __minimaal__ mogen zijn. Uitgangspunt van mijn onderzoek was mijn overtuiging dat bij verruiming van de wet, de bescherming van de proefpersonen wel gewaarborgd moet blijven. Want de eis van minimale risico__s en belasting mag dan problematisch zijn, maar met de onderliggende ethische redenering is niets mis: kinderen zouden in principe niet puur voor onderzoeksdoeleinden aan hoge risico__s en belasting moeten worden blootgesteld. Dankzij mijn multidisciplinaire begeleidingsgroep heb ik het onderwerp van verschillende kanten kunnen bekijken, en bevat het proefschrift niet alleen ethisch-theoretische artikelen, maar ook een analyse van de beslissingen van de centrale toetsingscommissie, een overzicht van de Europese regelgeving, en de verslagen van twee studies naar de wijze waarop kinderen verschillende onderzoeksprocedures ervaren. De conclusie is dat in geval van een __verfijning__ van de huidige wet, met als uitgangspunt een __bescherming op maat__, meer onderzoek mogelijk zou worden, en de bescherming van de proefpersonen eerder zou verbeteren dan verslechteren. Show less
The general aim of the studies described in this thesis is the effect evaluation of a family-based multidisciplinary cognitive behavioral treatment on several domains related to childhood obesity... Show moreThe general aim of the studies described in this thesis is the effect evaluation of a family-based multidisciplinary cognitive behavioral treatment on several domains related to childhood obesity compared to standard care. The main findings from these studies are a modest long-term reduction of both total and abdominal adiposity accompanied by improved physical fitness, while unchanged adiposity in the untreated controls led to decreased physical fitness and deteriorating insulin sensitivity. In addition, we found significantly impaired health related quality of life in the obese children compared to their normal weight peers. We showed that our multidisciplinary lifestyle treatment improved health related quality of life of the obese children after 1 year. We observed a significantly increased postprandial ghrelin response after the multidisciplinary treatment, but no effect on inflammatory markers, nor on gut hormones PYY and GLP-1. Finally, we propose an alternative for the definition of the metabolic syndrome in children, since the usefulness of its current dichotomous form is questionable. We show that a multivariate prediction model based on the individual components of the metabolic syndrome expressed as standard deviation scores (SDS) has a good predictive value regarding increased HOMA-IR SDS. Show less
