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Background: Synthesis of the hemostatic protein von Willebrand factor (VWF) drives formation of endothelial storage organelles called Weibel‐Palade bodies (WPBs). In the absence of VWF, angiogenic and inflammatory mediators that are costored in WPBs are subject to alternative trafficking routes. In patients with von Willebrand disease (VWD), partial or complete absence of VWF/WPBs may lead to additional bleeding complications, such as angiodysplasia. Studies addressing the role of VWF using VWD patient–derived blood outgrowth endothelial cells (BOECs) have reported conflicting results due to the intrinsic heterogeneity of patient‐derived BOECs. Objective: To generate a VWF‐deficient endothelial cell model using clustered regularly interspaced short palindromic repeats (CRISPR) genome engineering of blood outgrowth endothelial cells. Methods: We used CRISPR/CRISPR‐associated protein 9 editing in single‐donor cord blood–derived BOECs (cbBOECs) to generate clonal VWF−/− cbBOECs. Clones were selected using high‐throughput screening, VWF mutations were validated by sequencing, and cells were phenotypically characterized. Results: Two VWF−/− BOEC clones were obtained and were entirely devoid of WPBs, while their overall cell morphology was unaltered. Several WPB proteins, including CD63, syntaxin‐3 and the cargo proteins angiopoietin (Ang)‐2, interleukin (IL)‐6, and IL‐8 showed alternative trafficking and secretion in the absence of VWF. Interestingly, Ang‐2 was relocated to the cell periphery and colocalized with Tie‐2. Conclusions: CRISPR editing of VWF provides a robust method to create VWF‐ deficient BOECs that can be directly compared to their wild‐type counterparts. Results obtained with our model system confirmed alternative trafficking of several WPB proteins in the absence of VWF and support the theory that increased Ang‐2/Tie‐2 interaction contributes to angiogenic abnormalities in VWD patients.

Contains fulltext : 158770.pdf (publisher's version ) (Open Access), Today, more than half of the world population is under the age of 25 years and one in four is under age 18. The urgency of expanding access to Comprehensive Sexuality Education (CSE) notably for children and young people in Africa and Asia is greater than ever before. However, many challenges to the implementation and delivery of CSE in resource poor settings have been identified in the literature. CSE's effectiveness could be strongly improved if these challenges were better met. This paper aims to contribute to those much-needed improvements by sharing lessons learned from a decade of implementation of one particular CSE programme, The World Starts With Me, among various populations in 11 low income countries in Africa and Asia. The aims, content, reach and effectiveness of the programme are described. Next, the challenges for implementation and delivery at student, teacher, school and context level are discussed with reference to the wider knowledge base in this area. Finally, suggestions are provided for ways forward including the increased sensitivity of programmes for normative and practical barriers to sexual health, further advancement towards gender transformativity, a far-reaching expansion of comprehensive forms of teacher training and coaching, and a serious stepping-up of multilevel 'whole school' approaches.

Contains fulltext : 170048.pdf (publisher's version ) (Open Access), BACKGROUND: Ghana since 2004, begun implementation of a National Health Insurance Scheme (NHIS) to minimize financial barriers to health care at point of use of service. Usually health insurance is expected to offer financial protection to households. This study aims to analyze the effect health insurance on household out-of-pocket expenditure (OOPE), catastrophic expenditure (CE) and poverty. METHODS: We conducted two repeated household surveys in two regions of Ghana in 2009 and 2011. We first analyzed the effect of OOPE on poverty by estimating poverty headcount before and after OOPE were incurred. We also employed probit models and use of instrumental variables to analyze the effect of health insurance on OOPE, CE and poverty. RESULTS: Our findings showed that between 7-18 % of insured households incurred CE as a result of OOPE whereas this was between 29-36 % for uninsured households. In addition, between 3-5 % of both insured and uninsured households fell into poverty due to OOPE. Our regression analyses revealed that health insurance enrolment reduced OOPE by 86 % and protected households against CE and poverty by 3.0 % and 7.5 % respectively. CONCLUSION: This study provides evidence that high OOPE leads to CE and poverty in Ghana but enrolment into the NHIS reduces OOPE, provides financial protection against CE and reduces poverty. These findings support the pro-poor policy objective of Ghana's National Health Insurance Scheme and holds relevance to other low and middle income countries implementing or aiming to implement insurance schemes.

Contains fulltext : 145489.pdf (publisher's version ) (Closed access), This article uses data from Northern Tanzania to analyse how economic empowerment helps women reduce their reproductive health (RH) vulnerability. It analyses the effect of women's employment and economic contribution to their household on health care use at three phases in the reproductive cycle: before pregnancy, during pregnancy and at child birth. Economic empowerment shows a positive effect on health seeking behaviour during pregnancy and at child birth, which remains robust after controlling for bargaining power and selection bias. This indicates that any policy that increases women's economic empowerment can have a direct positive impact on women's RH.

Radboud Universiteit Nijmegen, 03 november 2015, Promotor : Ruben, R. Co-promotor : D'Exelle, B.S.H., Contains fulltext : 144369.pdf (publisher's version ) (Open Access)

Eighth Annual PopPov Conference on Population, Reproductive Health, and Economic Development, Nairobi, Kenya, 23 januari 2014, Item does not contain fulltext, While abundant evidence exists on the positive effect of women's empowerment on reproductive health, the inverse causality has been little studied. In this paper, we study the effects of reproductive health events on women's bodily integrity, using a panel data set of married women in Northern Tanzania. We find that pregnancy loss reduces women's rejection of intimate partner violence and that child mortality lowers women's perceived control over their sexual relationship with their husband. These results confirm the idea that women's bodily integrity is partly dependent on their reproductive role, i.e. the birth and lives of their children.

Contains fulltext : 54568.pdf (publisher's version ) (Closed access), This article addresses the question whether private aid agencies (PAAs) that operate in a market-like environment prefer to target different countries compared to their counterparts that operate in a more protected environment. The mainstream view is that competition for funds leads to a focus on middle-income countries where PAAs can easily obtain results. An alternative view considers PAA country choice more dependent on donor priorities. We collected data on aid allocation from 15 private agencies in Germany, Norway and the United States. The German organisations, which operate in the most protected environment, are least focused on the politically and economically poorly performing countries, whereas Norwegian and US-based private agencies show a higher degree of poor-country targeting. These results suggest that critics of marketisation may overestimate its pitfalls regarding country allocation. The poor-country targeting of PAAs proved to be related to the country choices made by bilateral donors, indicating the merit of the slipstream hypothesis.