Mutations in the CRB1 gene can cause retinal dystrophies such as Retinitis Pigmentosa or Leber Congenital Amaurosis . These patients experience progressive vision loss which ultimately leads to... Show moreMutations in the CRB1 gene can cause retinal dystrophies such as Retinitis Pigmentosa or Leber Congenital Amaurosis . These patients experience progressive vision loss which ultimately leads to blindness. Currently, there are no treatment options available for these patients.This thesis provides novel information on AAV.hCRB gene augmentation therapy in CRB1 mutant animal and human-derived models. We show the phenotype of (1) a novel mouse model with CRB2 ablation specifically in rod photoreceptor cells with loss of retinal function (Chapter 2), (2) a Crb1 mutant brown Norway rat with severe and early onset progressive vision loss (Chapter 3), (3) CRB1 patient-derived retinal organoids (Chapter 4), and (4) CRB1KO and CRB1KOCRB2+/- LCA-like retinal organoids (Chapter 5). Next, AAV-mediated gene augmentation was explored in Crb1 mutant rats (Chapter 3) and CRB1 patient-derived and CRB1KO LCA retinal organoids (Chapter 4 and 5). Finally, single-cell RNA sequencing was performed on AAV.hCRB treated CRB1 patient-derived retinal organoids (Chapter 4). To our knowledge this is the first time that an improved phenotype after AAV.hCRB gene augmentation in CRB1 RP patient-derived and CRB1KO LCA retinal organoids is observed, providing essential information for future gene therapy possibilities in patients with a mutation in the CRB1 gene. Show less
In this paper, we discuss practical challenges in ex-ante life cycle assessment (LCA) of emerging technologies, i.e., barriers to hands-on implementation, as opposed to the conceptual challenges... Show moreIn this paper, we discuss practical challenges in ex-ante life cycle assessment (LCA) of emerging technologies, i.e., barriers to hands-on implementation, as opposed to the conceptual challenges that recent contributions to the literature have been focusing on (see Giesen et al., 2020; Thonemann et al., 2020; Villares et al., 2017). We will illustrate the discussion with the case of emerging photovoltaics (PV), namely multijunction III-V/silicon tandem cell (III-V/Si). This case application helps structure the ex-ante LCA exercise and highlights the challenges of applying LCA early on in technology development, while providing sufficient general elements that apply to other emerging technologies.Written from the perspective of LCA analysts, the paper is organized around the LCA method. LCAs can be conducted at various stages of a technology development process, requiring different types of information at the various stages. By illustrating with the case study of emerging photovoltaics, the paper explores the importance of product performance optimization during technological development, and how it is directly linked to environmental performance during the use phase. It also demonstrates how the design and manufacturing choices that technology developers are confronted with can greatly influence environmental performance over the future product’s life cycle. The approach that emerges is one in which the LCA method remains flexible throughout the technology development process to accommodate its dynamic nature and the numerous uncertainties inherent in it. Show less
A framework for prospective/ex-ante life cycle assessment (LCA) and ecological risk assessment (ERA) of emerging technologies is developed and applied to a case study of III-V/silicon photovoltaic... Show moreA framework for prospective/ex-ante life cycle assessment (LCA) and ecological risk assessment (ERA) of emerging technologies is developed and applied to a case study of III-V/silicon photovoltaic panels. Show less
This dissertation is the culmination of over four years research on the rare earth element neodymium in the context of the 2010 REE crisis. Neodymium is a generally recognized ‘critical’... Show more This dissertation is the culmination of over four years research on the rare earth element neodymium in the context of the 2010 REE crisis. Neodymium is a generally recognized ‘critical’ material with a relevant application in the form of NdFeB magnets, both for sustainable energy technologies as well as the wider economy. This dissertation answers four main research questions: 1. What are the material flows of neodymium for NdFeB magnets, and how much can be made available for recycling? 2. What are the environmental burdens of NdFeB production, and how does recycling alleviate this burden? 3. What type of mechanisms along the NdFeB supply chain provide resilience in response to supply constraints and disruptions 4. Of all the possible resilience mechanisms, which played the largest role in the aftermath of the 2010 REE crisis? Besides directly answering the research question, this dissertation also reflects on the broader question of how actors in the NdFeB supply chain can change their behavior to limit their exposure to an unforeseen yet inevitable future crisis. Show less
National large-scale assessments have demonstrated a decrease in Dutch primary school students' performance on multidigit multiplication and division problems (e.g., 56x23 and 544:34) in the... Show moreNational large-scale assessments have demonstrated a decrease in Dutch primary school students' performance on multidigit multiplication and division problems (e.g., 56x23 and 544:34) in the past two decades. This performance decrease appears to be related to changes in students' use of mathematical strategies: the use of relatively accurate strategies for which calculations are written down has decreased, while the use of inaccurate mental strategies has increased. To gain more insight into these developments and how to possibly turn them around, factors that affect students' mathematical strategy use and performance were investigated. New applications of latent variable models to national large-scale assessment data were used to relate teachers' reports of their mathematics teaching to students' problem solving. Follow-up experiments were conducted at primary schools for a more controlled investigation of students' strategy choices and of how to influence those choices (and thereby, performance) favorably. It was found that teachers mainly influence students' choices between strategies with written work, and that they have less influence on choices for the inaccurate mental strategies (made more frequently by boys and weaker students). Extra instruction targeted at the latter was found to increase weaker students' choices for writing down calculations, and this improved students' performance. Show less
This thesis aims to evaluate the environmental sustainability of European imports of farmed aquatic food products from Asia, using life cycle assessment (LCA). Farming of Asian tiger prawn,... Show moreThis thesis aims to evaluate the environmental sustainability of European imports of farmed aquatic food products from Asia, using life cycle assessment (LCA). Farming of Asian tiger prawn, whiteleg shrimp, freshwater prawn, tilapia and pangasius catfish in Bangladesh, China, Thailand and Vietnam were chosen as representatives of the Asian aquaculture industry. Initial research revealed large discrepancies among LCA results driven by methodological choices and data sourcing. A protocol for quantifying dispersions around unit process data was therefore developed, characterising inherent uncertainty, spread (variability) and unrepresentativeness as the three major sources driving overall discrepancies. Results, propagated using Monte Carlo simulations, highlighted that the uncertainty related to LCA results could range with over an order of magnitude. For comparative purposes, however, only relative uncertainties are of relevance. Defining a hypothesis and using dependent sampling therefore allowed for several significant conclusions to be identified. Among these were significantly lower environmental impacts of Asian tiger shrimp farming in western Bangladesh, tilapia in Guangdong and pangasius in large-scale farms. Common environmental hot-spots included aqua-feeds, eutrophying effluents from farms, the use of benzalkonium chloride and other chlorine releasing compounds as disinfectants, and extensive use of paddle-wheels on shrimp farms. The research identified discrepancies Show less
