Purpose of Review Novel 3D organoid culture techniques have enabled long-term expansion of pancreatic tissue. This review comprehensively summarizes and evaluates the applications of primary tissue... Show morePurpose of Review Novel 3D organoid culture techniques have enabled long-term expansion of pancreatic tissue. This review comprehensively summarizes and evaluates the applications of primary tissue-derived pancreatic organoids in regenerative studies, disease modelling, and personalized medicine.Recent Findings Organoids derived from human fetal and adult pancreatic tissue have been used to study pancreas development and repair. Generated adult human pancreatic organoids harbor the capacity for clonal expansion and endocrine cell formation. In addition, organoids have been generated from human pancreatic ductal adenocarcinoma in order to study tumor behavior and assess drug responses.Summary Pancreatic organoids constitute an important translational bridge between in vitro and in vivo models, enhancing our understanding of pancreatic cell biology. Current applications for pancreatic organoid technology include studies on tissue regeneration, disease modelling, and drug screening. Show less
Several studies have highlighted the uniqueness of the human immune system in early life. Due to the scarceness of human fetal tissues and technical limitations, a system-wide and detailed... Show moreSeveral studies have highlighted the uniqueness of the human immune system in early life. Due to the scarceness of human fetal tissues and technical limitations, a system-wide and detailed phenotypical characterization of the composition and development of the human fetal immune system was lacking. Here, I delineate the composition and development of the human fetal immune system using an array of advanced high-throughput technologies. First, mass cytometry analysis of the innate lymphoid cells revealed a previously unrecognized subset named int-ILC in the fetal intestine, which can give rise to NK cells and ILC3s. Moreover, by combining the acquired datasets from (imaging-) mass cytometry, single-cell RNA-sequencing and TCR sequencing with advanced computational analysis tools and functional analysis this revealed that memory-like CD4+ T cells were already generated in the developing human fetal intestine, indicative of in utero exposure to foreign antigens. Additionally, (imaging-) mass cytometry analysis of the immune cells in the fetal intestine, spleen and liver revealed an early-life immune compartmentalization in these different fetal tissues. Overall, our results deepens the understanding of prenatal immunity and may ultimately be useful for the development of “early” intervention strategies to prevent the development of immune mediated diseases later in life. Show less
The workshop touched upon a multitude of topics. These can be subsumed under the following main headers:It included methodological considerations around doing comparative law and combining methods... Show moreThe workshop touched upon a multitude of topics. These can be subsumed under the following main headers:It included methodological considerations around doing comparative law and combining methods of comparative law with methods from other fields such as history, political science, sociology, computer science and accounting research.Empirically, it focused on understanding how a transplant process actually works and why it takes place, i.e. who the actors are that make a transplant happen. This included meso-level perspectives, focusing on actors such as bureaucracies, experts, lawmakers, companies, accounting firms and others, but also perspectives which focused more on states as a whole and their role as norm makers and takers. The analyses thereby drew from experiences from many different countries around the world and included a number of historical perspectives as well. The participants also discussed evidence on the extent to which convergence is occurring, using the example of the tax treaty system and the implementation of the BEPS standards.Theoretically, several key concepts were discussed such as the notion of “expertise”, “international standard”, the concept of “transplant” itself and possible alternative metaphors as well as the history of the idea. It was also examined how one can approach the empirical fact of transplants or international convergence of rules from a normative and philosophical point of view.This document reports the discussions that took place during the five days in a chronological manner. The last section contains an outline of possible topics and approaches for a follow-up workshop.The report does not systematically differentiate between individual opinions that not everyone might share and consensus. It rather reports which bits and pieces of the debates caught the attention of the reporters and other note takers. It may therefore rather be seen as something stimulating further discussion than a fixed document. Show less
Klapwijk, E.T.; Van de Kamp, F.; Meulen, M. van der; Peters, S.; Wierenga, L.M. 2019
Performing quality control to detect image artifacts and data-processing errors is crucial in structural magnetic resonance imaging, especially in developmental studies. Currently, many studies... Show morePerforming quality control to detect image artifacts and data-processing errors is crucial in structural magnetic resonance imaging, especially in developmental studies. Currently, many studies rely on visual inspection by trained raters for quality control. The subjectivity of these manual procedures lessens comparability between studies, and with growing study sizes quality control is increasingly time consuming. In addition, both inter-rater as well as intra-rater variability of manual quality control is high and may lead to inclusion of poor quality scans and exclusion of scans of usable quality. In the current study we present the Qoala-T tool, which is an easy and free to use supervised-learning model to reduce rater bias and misclassification in manual quality control procedures using FreeSurfer-processed scans. First, we manually rated quality of N = 784 FreeSurfer-processed T1-weighted scans acquired in three different waves in a longitudinal study. Different supervised-learning models were then compared to predict manual quality ratings using FreeSurfer segmented output data. Results show that the Qoala-T tool using random forests is able to predict scan quality with both high sensitivity and specificity (mean area under the curve (AUC) = 0.98). In addition, the Qoala-T tool was also able to adequately predict the quality of two novel unseen datasets (total N = 872). Finally, analyses of age effects showed that younger participants were more likely to have lower scan quality, underlining that scan quality might confound findings attributed to age effects. These outcomes indicate that this procedure could further help to reduce variability related to manual quality control, thereby benefiting the comparability of data quality between studies. Show less
Adolescence has been described as a unique period for self-concept development, with an intensified alertness to social comparison as a mechanism for self-knowledge and self-evaluation. However, it... Show moreAdolescence has been described as a unique period for self-concept development, with an intensified alertness to social comparison as a mechanism for self-knowledge and self-evaluation. However, it remains difficult to disentangle the specific influence of these social comparisons on the development of self-descriptions in adolescence. Moreover, it is still unclear how social comparisons impact upon the development of self-views in different domains, such as physical, academic and social self-views. The goal of this study was therefore to examine the development of self-descriptions in different domains across adolescence, and to experimentally test how the development of these self-descriptions is altered by an explicit social comparison context. For this purpose, we developed two tasks which both asked participants (aged 9-25-years, N = 202) for trait self-descriptions but differed in the salience of a social comparison. Results showed consistent age-differences with more positive self-views for children and adolescents in the age-range 9–14 years. The context of explicit social comparison yielded similar as well as additional age-differences that were more dependent upon valence and domain. Moreover, mid-adolescents (15–17 y) were most negatively affected by these social comparisons relative to other ages. Together, this study made a first step in disentangling the specific influence of social comparison outcomes within the development of general self-descriptions, and highlights the importance of social context in studying self-concept in adolescence. Show less
There has been a large spike in longitudinal fMRI studies in recent years, and so it is essential that researchers carefully assess the limitations and challenges afforded by longitudinal designs.... Show moreThere has been a large spike in longitudinal fMRI studies in recent years, and so it is essential that researchers carefully assess the limitations and challenges afforded by longitudinal designs. In this article, we provide an overview of important considerations for longitudinal fMRI research in developmental samples, including task design, sampling strategies, and group-level analyses. We first discuss considerations for task designs, weighing the pros and cons of many commonly used tasks, as well as outlining how the tasks may be impacted by repeated exposure. Secondly, we review the types of group-level analyses that can be conducted on longitudinal fMRI data, analyses which must account for repeated measures. Finally, we review and critique recent longitudinal studies that have emerged in the past few years. Show less
A key process in the life of any multicellular organism is its development from a single egg into a full grown adult. The first step in this process often consists of forming a tissue layer out of... Show moreA key process in the life of any multicellular organism is its development from a single egg into a full grown adult. The first step in this process often consists of forming a tissue layer out of randomly placed cells on the surface of the egg. We present a model for generating such a tissue, based on mechanical interactions between the cells, and find that the resulting cellular pattern corresponds to the Voronoi tessellation of the nuclei of the cells. Experimentally, we obtain the same result in both fruit flies and flour beetles, with a distribution of cell shapes that matches that of the model, without any adjustable parameters. Finally, we show that this pattern is broken when the cells grow at different rates. Show less
Constructing a knowledge representation from multiple texts requires the integration of information across texts. The aim of the current study was to investigate how elementary school students... Show moreConstructing a knowledge representation from multiple texts requires the integration of information across texts. The aim of the current study was to investigate how elementary school students integrate information across multiple text passages and, particularly, whether students use information from a prior text to improve understanding of a current text. A sample of 105 children in grades 4 and 6 participated in the experiment. The multiple-text integration paradigm was used to study integration processes across texts during reading. Recall and (application) questions were used to investigate the extent to which information from different text passages was integrated into knowledge representations after reading. Individual differences in reading comprehension ability and working memory were also considered. The results indicate that children in both grades spontaneously activate information from an earlier text to aid their understanding during reading, and that they integrate information across texts in their knowledge representations. This was the case regardless of grade or individual differences in reading-comprehension ability and working memory. These findings provide insight into the mechanisms that may be involved in the integration of information across texts. Show less
Many hunter-gatherer groups live on the outskirts of wider society, experiencing poor health outcomes with little access to medical care. From a development perspective, key interventions include... Show moreMany hunter-gatherer groups live on the outskirts of wider society, experiencing poor health outcomes with little access to medical care. From a development perspective, key interventions include the sedentarisation of these mobile peoples into camps nearby larger towns with sanitation infrastructure and medical care, as increased access to services is assumed to improve outcomes. However, recent research in the Agta (Philippine foragers from North-east Luzon) has demonstrated that individuals residing in more ‘developed’ communities suffer from increased morbidity and mortality. Here, using quantitative and ethnographic data on health collected between 2002 and 2014, we explore why this trend occurs by examining the relationship between key development initiatives with self-reported illness and the uptake of medical interventions with 415 Agta men, women and children. We demonstrate that health outcomes worsen as sedentarisation progresses, despite some increases in medical access. We argue this is because the development paradigm is not evidence-based, but rather stems from an ideological dislike of mobile hunter-gatherer lifestyles. Compounded by cultural insensitivity and daily discrimination, current interventions are ill-suited to the unique needs of hunter-gatherers, and thus ineffective. Based on our findings we offer future short and long-term policy suggestions which seek to reduce the Agta's vulnerability, rather than increase it. Show less
Van der Cruijsen, R.; Peters, S.; Aar, L.P.E. van der; Crone, E.A. 2018
Neuroimaging studies in adults showed that cortical midline regions including medial prefrontal cortex (mPFC) and posterior parietal cortex (PPC) are important in self-evaluations. The goals of... Show moreNeuroimaging studies in adults showed that cortical midline regions including medial prefrontal cortex (mPFC) and posterior parietal cortex (PPC) are important in self-evaluations. The goals of this study were to investigate the contribution of these regions to self-evaluations in late childhood, adolescence, and early adulthood, and to examine whether these differed per domain (academic, physical and prosocial) and valence (positive versus negative). Also, we tested whether this activation changes across adolescence. For this purpose, participants between ages 11–21-years (N = 150) evaluated themselves on trait sentences in an fMRI session. Behaviorally, adolescents rated their academic traits less positively than children and young adults. The neural analyses showed that evaluating self-traits versus a control condition was associated with increased activity in mPFC (domain-general effect), and positive traits were associated with increased activity in ventral mPFC (valence effect). Self-related mPFC activation increased linearly with age, but only for evaluating physical traits. Furthermore, an adolescent-specific decrease in striatumactivation for positive self traits was found. Finally, we found domain-specific neural activity for evaluating traits in physical (dorsolateral PFC, dorsal mPFC) and academic (PPC) domains. Together, these results highlight the importance of domain distinctions when studying self-concept development in late childhood, adolescence, and early adulthood. Show less
Mensen, V.T.; Wierenga, L.M.; Dijk, S. van; Rijks, Y.; Oranje, B.; Mandl, R.C.W.; Durston, S. 2017
In this thesis we aimed to get insight in how the methylome is established during development and subsequently degenerates during ageing using an integrative approach to the analysis of DNA... Show moreIn this thesis we aimed to get insight in how the methylome is established during development and subsequently degenerates during ageing using an integrative approach to the analysis of DNA methylation in conjunction with other levels of genomics data. The first two empirical chapters of this thesis describe the establishment and the maintenance of the epigenome during fetal development and in later life in multiple tissues. In the subsequent two chapters we investigated the loss of control over the methylome in blood and other tissues. Show less
ABSTRACT In reflection upon the worthy work of Professor Shinya Konaka and his col- leagues, this contribution discusses the idea of “Localization of Humanitarian Assistance”. Several critical... Show moreABSTRACT In reflection upon the worthy work of Professor Shinya Konaka and his col- leagues, this contribution discusses the idea of “Localization of Humanitarian Assistance”. Several critical questions arise from a humanitarian situation where the needs are assessed: we have to know what people need and what they don’t need. We need to determine coping mech- anisms that need not substituted but rather facilitated. To not undermine and further marginal- ize we need to know what resources, skills and social capital East African pastoralists have and how they are activated, where and when. The discussion is organized in observations from on one hand, archaeological and heritage perspective and on the other, personal experience of refugees and IDP life in the East Africa. It concludes that people do not only need food and shelter to survive and that cultural heritage is a basic human need too. Without the traditional skills and coping mechanisms that are inherent in the cultural values that glue people together, it is difficult for East African pastoralists to survive. Violence and neglect against people and environment are related to the destruction and neglect of cultural and natural heritage, which are people’s means of livelihood and sources of identity and dignity. Show less
Gurp, L. van; Loomans, C.J.M.; Krieken, P.P. van; Dharmadhikari, G.; Jansen, E.; Ringnalda, F.C.A.S.; ... ; Koning, E.J.P. de 2016
International nongovernmental organizations (INGOs) provide essential aid and public services to less-developed countries. Although most literature focuses on Western INGOs, Asian INGOs have also... Show moreInternational nongovernmental organizations (INGOs) provide essential aid and public services to less-developed countries. Although most literature focuses on Western INGOs, Asian INGOs have also become globally active. Little is known about what motivates INGOs to provide services in other regions, such as Latin America. In this study, we seek to identify the criteria Japanese INGOs use to select Latin American recipient countries. We propose that Japanese INGO operational location decisions are a function of Japanese foreign policy agenda, Japan-recipient country business relations, and recipient country’s need and liberalization. Using data from Japanese INGOs working in Latin America and 24 Latin American countries on contextual, macroeconomic, and demographic indicators, we find that the significant factors driving INGO decisions to operate in Latin American countries are need and the presence of Japanese businesses in the recipient country. Results have practical implications for foreign aid targeting and economic development. Show less
