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T helper 17 cells and Regulatory T cells in Pulmonary Sarcoidosis: It takes two to tangle Caroline Elizabeth Broos Sarcoidosis is an intriguingly complex immunological disorder. It is characterized by the formation of non-necrotizing granulomas that are most commonly found in the mediastinal lymph nodes and lungs of patients. Gaps in knowledge on sarcoidosis disease etiology and determinants of disease course have thus far impeded rational decisions on ‘Who, When and How’ to treat. The mainstay of sarcoidosis therapy remains immunosuppressive, using relatively high doses of systemic prednisone. However, although often effective, corticosteroid treatment can be accompanied by severe side effects. Detailed insight in the immunological response occurring in pulmonary sarcoidosis patients can help find determinants of disease etiology and disease course, which can yield new therapeutic targets. Therefore, the first aim of this thesis is to further unravel the immune-related pathogenesis of pulmonary sarcoidosis. The second aim is to gain insight into current prednisone treatment, in order to optimize treatment strategies to reduce side effects and increase quality of life of pulmonary sarcoidosis patients. Findings described in this thesis provide a new perspective on sarcoidosis pathogenesis, challenging long-held paradigms and exploring novel approaches to further unravel this immunological complex disease. Furthermore, a rationale is provided to evaluate the potential of certain existing therapies that are currently used in other autoimmune diseases for pulmonary sarcoidosis treatment. Finally, results of this thesis lay a strong foundation for future studies that can help individualize sarcoidosis treatment and thereby increase pulmonary sarcoidosis-related quality of care and patient-related quality of life. https://graphik-buro.nl/epub/carolinebroos/ #proefschrift #drukwerk #drukken #epub #ebook #digital #publication #dissertatie #dissertation #phd #university #layout #opmaak #design #promovendi #promovendus #ontwerp #print #offset #oreader #pdf #proefschriften #artikel #vormgeving #typography #typografie #letterkunde #grafisch #graphicdesign #graphic

Digitale publicatie. Een wereld van mogelijkheden. https://graphik-buro.nl/

Preclinics and clinics of neuroendocrine tumors: Prekliniek en kliniek van neuroendocriene tumoren Roxanne van Adrichem Neuroendocrine tumors (NETs) are considered rare tumors. About 70% of all NETs will develop in the gastroenteropancreatic (GEP) system and are named GEP NETs. Currently used circulating biomarkers like serum chromogranin A and neuron-specific enolase have major limitations. Furthermore, therapeutic options are limited. GEP NETs may escape from medical treatment by tachyphylaxis and/or the development of resistance and patients will eventually develop progressive disease. The main aims of this thesis were to: 1) improve the diagnostic work-up and follow-up of GEP NET patients using sensitive and specific tumor markers and, 2) to identify new biotherapeutical options by modulating pathological pathways in pancreatic NET cells. https://graphik-buro.nl/epub/roxannevanadrichem/ #proefschrift #drukwerk #drukken #epub #ebook #digital #publication #dissertatie #dissertation #phd #university #layout #opmaak #design #promovendi #promovendus #ontwerp #print #offset #oreader #pdf #proefschriften #artikel #vormgeving #typography #typografie #letterkunde #grafisch #graphicdesign #graphic

Prognostic factors, treatment goals and clinical endpoints in pediatric pulmonary arterial hypertension Mark-Jan Ploegstra Pulmonale arteriële hypertensie (PAH) is een progressieve levensbedreigende ziekte van de longslagaders en wordt geïntroduceerd in Hoofdstuk 1 van dit proefschrift. Bij PAH zorgt de toegenomen bloeddruk in het longvaatbed voor een overbelasting van de rechter hartkamer, wat leidt tot hartfalen van de rechter hartkamer en uiteindelijk tot de dood. Ondanks grote stappen die de afgelopen decennia zijn gemaakt in de behandelmogelijkheden voor volwassenen, is PAH op de kinderleeftijd nog steeds een verwoestende ongeneeslijke ziekte. De sterftecijfers zijn vooral bij kinderen onbevredigend, en dienen te worden verbeterd. https://graphik-buro.nl/epub/markjanploegstra/ #proefschrift #drukwerk #drukken #epub #ebook #digital #publication #dissertatie #dissertation #phd #university #layout #opmaak #design #promovendi #promovendus #ontwerp #print #offset #oreader #pdf #proefschriften #artikel #vormgeving #typography #typografie #letterkunde #grafisch #graphicdesign #graphic

Vechtscheidingen Onderzoeksrapport In Nederland lijken we steeds vaker geconfronteerd te worden met vechtscheidingen. Regelmatig horen we via de media over tragische gezinsdrama’s 1 waarin een vechtscheiding een grote rol speelde. Zoals bijvoorbeeld de casus Zeist, waarbij er sprake was van een problematische scheiding, waar vader door suïcide om het leven komt en wordt verdacht van het ombrengen van zijn twee zoons (Casusonderzoek Zeist, 2013). Ook uit voorlichtingscampagnes die netwerkpartners oproepen om te helpen bij het verzachten van de strijd tussen ouders (Ministerie van Volksgezondheid, Welzijn en Sport, 2015), blijkt dat deze problematiek nijpend is en om een oplossing vraagt. Vechtscheidingen zijn vooral een probleem, omdat kinderen inzet worden van de strijd, daardoor in de knel komen, met als resultaat dat hun welzijn en optimale ontwikkeling door de conflicten tussen ouders ernstig belemmerd wordt (Dullaert, 2014). Dit wordt bijvoorbeeld duidelijk in het eerder genoemde rapport ‘Casusonderzoek Zeist’ dat spreekt over “een scheiding die gepaard gaat met hevige spanningen en conflicten tussen ouders, waardoor ouders niet meer in staat zijn om het belang van hun kinderen voorop te stellen” (Casusonderzoek Zeist, 2013, p. 35, noot 11). Een oplossing is echter niet gemakkelijk gevonden. Zowel hulpverleners als onderzoekers doen veel moeite om meer grip te krijgen op de complexiteit van deze doelgroep en de benodigde hulpverlening. https://graphik-buro.nl/epub/vechtscheidingen/ #proefschrift #drukwerk #drukken #epub #ebook #digital #publication #dissertatie #dissertation #phd #university #layout #opmaak #design #promovendi #promovendus #ontwerp #print #offset #oreader #pdf #proefschriften #artikel #vormgeving #typography #typografie #letterkunde #grafisch #graphicdesign #graphic

Small Airways Disease in Cystic Fibrosis: Improving Efficacy of Treatment Aukje Bos The studies described in this thesis are focused on the efficiency of inhaled drugs in patients with cystic fibrosis (CF). We mainly aimed to improve treatment of small airway disease. https://graphik-buro.nl/epub/aukjebos/ #proefschrift #drukwerk #drukken #epub #ebook #digital #publication #dissertatie #dissertation #phd #university #layout #opmaak #design #promovendi #promovendus #ontwerp #print #offset #oreader #pdf #proefschriften #artikel #vormgeving #typography #typografie #letterkunde #grafisch #graphicdesign #graphic

Esophageal Adenocarcinoma, More Than One Entity? A. van Nistelrooij This thesis highlighted that the population of EAC patients appears to be relatively heterogeneous, including patients with sporadic cancers, patients with a positive family history for EAC and BE, and young aged patients. The aim of this thesis was to elucidate the molecular biology of EAC by performing standard molecular analysis, i.e. whole- exome sequencing, targeted sequencing and Sanger sequencing on sporadic, familial and young EAC cases. In addition, clinicopathological features of families with clustering of EAC and BE and young individuals with EAC were studied. https://graphik-buro.nl/epub/annavannistelrooij/ #proefschrift #drukwerk #drukken #epub #ebook #digital #publication #dissertatie #dissertation #phd #university #layout #opmaak #design #promovendi #promovendus #ontwerp #print #offset #oreader #pdf #proefschriften #artikel #vormgeving #typography #typografie #letterkunde #grafisch #graphicdesign #graphic

Perioperative inflammation and hypotension T. Rettig Each year over 1.4 million surgical procedures are performed in the Netherlands. In general, surgery is considered safe by doctors and their patients. However, outcome can vary greatly between different types of surgery. For example, complications are common after major surgery. The negative impact of postoperative complications on long-term outcome is of significant concern to patients and their clinicians. The pathophysiological mechanisms of complications after surgery, however, are largely unknown. This thesis describes the relation between two possible determinants of adverse events after major surgery: perioperative inflammation and hypotension. https://graphik-buro.nl/epub/thijsrettig/ #proefschrift #drukwerk #drukken #epub #ebook #digital #publication #dissertatie #dissertation #phd #university #layout #opmaak #design #promovendi #promovendus #ontwerp #print #offset #oreader #pdf #proefschriften #artikel #vormgeving #typography #typografie #letterkunde #grafisch #graphicdesign #graphic

Sturen op verbinden: De business case van diversiteit van publieke organisaties S. Çelik Al tientallen jaren streeft de Nederlandse overheid naar diversiteit binnen haar organisatie. Of het nu gaat om de politie of het onderwijs, de waterschappen of de departementen, nagenoeg alle onderdelen van de publieke sector willen de verschillen benutten om de effectiviteit van de overheid te vergroten. De business case van diversiteit zit dus geworteld in het denken binnen de publieke sector. Vreemd genoeg wordt dit bewustzijn slechts in beperkte mate omgezet in interventies die bijdragen aan een overheid die adequaat maatschappelijke problemen kan oplossen. De uitdaging voor publieke organisaties ligt vooral in het duurzaam verbinden van de overheid met de samenleving. Sturen op verbinden kan het vertrouwen van burgers in de overheid vergroten. Dat kan bijvoorbeeld door zo goed mogelijk in het personeelsbestand een weerspiegeling te creëren van de samenleving. Maar zeker ook door de wisselwerking tussen de overheid en burgers, én binnen de overheid te stimuleren. Bovendien vergroten de juiste business case interventies de binding van medewerkers met de publieke organisaties. Transformationeel leiderschap en een inclusieve organisatiecultuur spelen daarbij een cruciale rol. Dit proefschrift toont aan dat sturen op verbinden de nieuwe route is voor de publieke sector. https://graphik-buro.nl/epub/saniyecelik/ #proefschrift #drukwerk #drukken #epub #ebook #digital #publication #dissertatie #dissertation #phd #university #layout #opmaak #design #promovendi #promovendus #ontwerp #print #offset #oreader #pdf #proefschriften #artikel #vormgeving #typography #typografie #letterkunde #grafisch #graphicdesign #graphic

Medication Adherence In Children With Asthma Erwin Vasbinder Asthma is a highly prevalent chronic disease in children and is associated with impairment of quality of life and considerable healthcare use and costs. Many interventions for improving medication adherence have been studied, but the effect on medication adherence were generally small and varied between adherence measures. Only few studies have reported effects on both adherence and treatment outcomes. This thesis aims to investigate opportunities for identifying and reducing non-adherence to ICS in children with asthma in The Netherlands. The research questions were: What is the clinical relevance of non-adherence to ICS? What is the role of ethnicity as a risk-factor for non-adherence? Can Real Time Medication Monitoring with tailored SMS-reminders improve adherence to ICS, asthma control, asthma-related quality of life and the risk of asthma exacerbations? What is the role of asthma self-management by children in daily life? Are patient-reported adherence and refill-adherence suitable methods for identifying children who are non-adherent to ICS? https://graphik-buro.nl/epub/erwinvasbinder/ #proefschrift #drukwerk #drukken #epub #ebook #digital #publication #dissertatie #dissertation #phd #university #layout #opmaak #design #promovendi #promovendus #ontwerp #print #offset #oreader #pdf #proefschriften #artikel #vormgeving #typography #typografie #letterkunde #grafisch #graphicdesign #graphic

The genetics of carotid atherosclerosis: Associations with clinical outcome and histological plaque characteristics Sander W. van der Laan At the turn of this century a first draft of the human genome sequence was presented. This ushered in an unprecedented era of scientific work focused on the genetics of complex traits and common disease. In this work, the author and his peers endeavored to understand the complex genetics of carotid atherosclerosis. They further sought human evidence to validate atherosclerotic genes discovered in experimental models, and investigated the putative causality of a presumptive biomarker. https://graphik-buro.nl/epub/sandervanderlaan/ #proefschrift #drukwerk #drukken #epub #ebook #digital #publication #dissertatie #dissertation #phd #university #layout #opmaak #design #promovendi #promovendus #ontwerp #print #offset #oreader #pdf #proefschriften #artikel #vormgeving #typography #typografie #letterkunde #grafisch #graphicdesign #graphic

Acquired Demyelinating Syndromes: Focus on Neuromyelitis Optica and childhood-onset Multiple Sclerosis Danielle van Pelt Acquired Demyelinating Syndromes (ADS) cover a broad spectrum of inflammatory demyelinating syndromes in the CNS, of which multiple sclerosis (MS) is the most common subtype. This thesis focuses on two relatively rare clinical subtypes of ADS: Neuromyelitis Optica Spectrum Disorders (NMOSD) and childhood-onset ADS including MS. Awareness and recognition of uncommon ADS subtypes are of importance for clinicians, since those require a distinct diagnostic and therapeutic approach. In this thesis we aimed to reveal the spectrum of ADS by describing the clinical features of NMOSD and childhood-onset ADS, in order to improve the diagnostic process. https://graphik-buro.nl/epub/daniellevanpelt/ #proefschrift #drukwerk #drukken #epub #ebook #digital #publication #dissertatie #dissertation #phd #university #layout #opmaak #design #promovendi #promovendus #ontwerp #print #offset #oreader #pdf #proefschriften #artikel #vormgeving #typography #typografie #letterkunde #grafisch #graphicdesign #graphic

Unloading the osteoarthritic knee: osteotomy and joint distraction Jan Ton van der Woude In the young and active population results after knee replacement are less satisfactory with higher rates of revision due to mechanical, aseptic loosening. Therefore, in case of persisting, painful, conservative treatment-resistant knee osteoarthritis at relative young age, alternative, joint preserving, treatments strategies are a necessity. In this population the surgical treatment should focus on reversing the mechanical factors associated with the development and progression of knee osteoarthritis. An option in this respect is (temporarily) unloading the knee joint. Depending on the severity of the osteoarthritis (unicompartmental or bicompartmental) and malalignment, unloading of the knee joint is possible by performing an osteotomy (partial unloading) or by knee joint distraction (temporarily unloading). Therefore, this thesis aimed to improve the knowledge regarding knee joint preserving treatments, such as valgus-producing distal femoral osteotomy (DFO) and knee joint distraction (KJD). In this way a better understanding of what the optimal treatment will be in relatively young patients with conservative treatment-resistant knee osteoarthritis may be found. https://graphik-buro.nl/epub/jantonvanderwoude/ #proefschrift #drukwerk #drukken #epub #ebook #digital #publication #dissertatie #dissertation #phd #university #layout #opmaak #design #promovendi #promovendus #ontwerp #print #offset #oreader #pdf #proefschriften #artikel #vormgeving #typography #typografie #letterkunde #grafisch #graphicdesign #graphic

Restore The Balance: Side effects of dexamethasone in children with acute lymphoblastic leukemia Lidewij Warris Synthetic glucocorticoids, such as dexamethasone and prednisolone, are widely and successfully used as anti-leukemic agents like in the Dutch treatment protocols for pediatric acute lymphoblastic leukemia (ALL). Dexamethasone is considered to be the preferred glucocorticoid based on its higher anti-leukemic activity and central nervous system penetration.1 However, the use of glucocorticoids, and especially dexamethasone, is notorious for various side effects, like metabolic and neuropsychological side effects. Neuropsychological side effects are experienced as the most detrimental to the quality of life by patients and their caregivers. Since most pediatric ALL patients receive dexamethasone courses during at least one and a half year, these side effects have a high impact on the daily life and development. To date, therapeutic interventions to avoid dexamethasone-induced neuropsychological side effects are scarce, and limited to anti-depressive agents and antipsychotics. Therefore, there is a strong need for novel interventions to reduce these side effects. In this thesis we studied the efficacy of hydrocortisone as intervention for dexamethasone-induced neuropsychological side effects, based on the hypothesis that the neuropsychological side effects are due to cortisol depletion of the mineralocorticoid receptor (MR) caused by dexamethasone. https://graphik-buro.nl/epub/lidewijwarris/ #proefschrift #drukwerk #drukken #epub #ebook #digital #publication #dissertatie #dissertation #phd #university #layout #opmaak #design #promovendi #promovendus #ontwerp #print #offset #oreader #pdf #proefschriften #artikel #vormgeving #typography #typografie #letterkunde #grafisch #graphicdesign #graphic

Optimization of Care Strategies in Hemophilia J. Lock The aims of this thesis were to study strategies that may further improve patient outcome in hemophilia, by optimization of both patient care by interventions in adherence as well as treatment innovations. https://graphik-buro.nl/epub/janskelock #proefschrift #drukwerk #drukken #epub #ebook #digital #publication #dissertatie #dissertation #phd #university #layout #opmaak #design #promovendi #promovendus #ontwerp #print #offset #oreader #pdf #proefschriften #artikel #vormgeving #typography #typografie #letterkunde #grafisch #graphicdesign #graphic

Samengesteld besturen: De kracht en kwetsbaarheid van duale besturing in algemene ziekenhuizen Linda Muijsers-Creemers Samengesteld besturen bevat geen ‘kant-en-klare besturingsrecepten’. De lezer mag zelf de verbinding leggen tussen het unieke van de casussen, de analyse van de besturingsarrangementen én de eigen situatie. Het onderzoek biedt daarmee informatie voor bestuurders, managers, medici, beleidsmedewerkers, toezichthouders, beleidsmakers en consultants die zich bezig houden met de besturing van het ziekenhuis. https://graphik-buro.nl/epub/lindamuijsers/ #proefschrift #drukwerk #drukken #epub #ebook #digital #publication #dissertatie #dissertation #phd #university #layout #opmaak #design #promovendi #promovendus #ontwerp #print #offset #oreader #pdf #proefschriften #artikel #vormgeving #typography #typografie #letterkunde #grafisch #graphicdesign #graphic