(RB1)-negative retinal organoids display proliferation of cone photoreceptors and loss of retinal differentiation

Retinoblastoma is a tumor of the eye in children under the age of five caused by biallelic inactivation of the (RB1) tumor suppressor gene in maturing retinal cells. Cancer models are essential for understanding tumor development and in preclinical research. Because of the complex organization of the human retina, such models were challenging to develop for retinoblastoma. Here, we present an organoid model based on differentiation of human embryonic stem cells into neural retina after inactivation of (RB1) by CRISPR/Cas9 mutagenesis. Wildtype and (RB1) heterozygous mutant retinal organoids were indistinguishable with respect to morphology, temporal development of retinal cell types and global mRNA expression. However, loss of pRB resulted in spatially disorganized organoids and aberrant differentiation, indicated by disintegration of organoids beyond day 130 of differentiation and depletion of most retinal cell types. Only cone photoreceptors were abundant and continued to proliferate, supporting these as candidate cells-of-origin for retinoblastoma. Transcriptome analysis of (RB1) knockout organoids and primary retinoblastoma revealed gain of a retinoblastoma expression signature in the organoids, characterized by upregulation of (RBL1) (p107), (MDM2), (DEK), (SYK) and (HELLS). In addition, genes related to immune response and extracellular matrix were specifically upregulated in (RB1)-negative organoids. In vitro retinal organoids therefore display some features associated with retinoblastoma and, so far, represent the only valid human cancer model for the development of this disease

How many educated workers for your economy? European targets, optimal public spending, and labor market impact

This paper studies optimal taxation schemes for education in a search- matching model where the labor market is divided between a high-skill and a low-skill sector. Two public policy targets - maximizing the total employment level and optimizing the social surplus - are studied according to three different public taxation strategies. We calibrate our model using evidence from thirteen European countries, and compare our results with the target from the Europe 2020 Agenda for achievement in higher education. We show that, with current labor market char- acteristics, the target set by governments seems compatible with the social surplus maximization objective for some countries, while being too high for other countries. For all countries, maximizing employment would imply higher educational spending than that required for the social surplus to reach its maximum.info:eu-repo/semantics/publishedVersio

The equity impact vaccines may have on averting deaths and medical impoverishment in developing countries

With social policies increasingly directed toward enhancing equity through health programs, it is important that methods for estimating the health and economic benefits of these programs by subpopulation be developed, to assess both equity concerns and the programs’ total impact. We estimated the differential health impact (measured as the number of deaths averted) and household economic impact (measured as the number of cases of medical impoverishment averted) of ten antigens and their corresponding vaccines across income quintiles for forty-one low- and middle-income countries. Our analysis indicated that benefits across these vaccines would accrue predominantly in the lowest income quintiles. Policy makers should be informed about the large health and economic distributional impact that vaccines could have, and they should view vaccination policies as potentially important channels for improving health equity. Our results provide insight into the distribution of vaccine-preventable diseases and the health benefits associated with their prevention

Has decentralisation affected child immunisation status in Indonesia?

Background: The past two decades have seen many countries, including a number in Southeast Asia, decentralising their health system with the expectation that this reform will improve their citizens’ health. However, the consequences of this reform remain largely unknown. Objective: This study analyses the effects of fiscal decentralisation on child immunisation status in Indonesia. Design: We used multilevel logistic regression analysis to estimate these effects, and multilevel multiple imputation to manage missing data. The 2011 publication of Indonesia's national socio-economic survey (Susenas) is the source of household data, while the Podes village census survey from the same year provides village-level data. We supplement these with local government fiscal data from the Ministry of Finance. Results: The findings show that decentralising the fiscal allocation of responsibilities to local governments has a lack of association with child immunisation status and the results are robust. The results also suggest that increasing the number of village health centres (posyandu) per 1,000 population improves probability of children to receive full immunisation significantly, while increasing that of hospitals and health centres (puskesmas) has no significant effect. Conclusion: These findings suggest that merely decentralising the health system does not guarantee improvement in a country's immunisation coverage. Any successful decentralisation demands good capacity and capability of local governments

'Communicate to vaccinate' (COMMVAC). building evidence for improving communication about childhood vaccinations in low- and middle-income countries: protocol for a programme of research

ABSTRACT: BACKGROUND: Effective provider-parent communication can improve childhood vaccination uptake and strengthen immunisation services in low- and middle-income countries (LMICs). Building capacity to improve communication strategies has been neglected. Rigorous research exists but is not readily found or applicable to LMICs, making it difficult for policy makers to use it to inform vaccination policies and practice. The aim of this project is to build research knowledge and capacity to use evidence-based strategies for improving communication about childhood vaccinations with parents and communities in LMICs. Methods and design This project is a mixed methods study with six sub-studies. In sub-study one, we will develop a systematic map of provider-parent communication interventions for childhood vaccinations by screening and extracting data from relevant literature. This map will inform sub-study two, in which we will develop a taxonomy of interventions to improve provider-parent communication around childhood vaccination. In sub-study three, the taxonomy will be populated with trial citations to create an evidence map, which will also identify how evidence is linked to communication barriers regarding vaccination. In the project's fourth sub-study, we will present the interventions map, taxonomy, and evidence map to international stakeholders to identify high-priority topics for systematic reviews of interventions to improve parent-provider communication for childhood vaccination. We will produce systematic reviews of the effects of high-priority interventions in the fifth sub-study. In the sixth and final sub-study of the project, evidence from the systematic reviews will be translated into accessible formats and messages for dissemination to LMICs. DISCUSSION: This project combines evidence mapping, conceptual and taxonomy development, priority setting, systematic reviews, and knowledge transfer. It will build and share concepts, terms, evidence, and resources to aid the development of communication strategies for effective vaccination programmes in LMIC

Inequitable childhood immunization uptake in Nigeria: a multilevel analysis of individual and contextual determinants

Background: Immunization coverage in many parts of Nigeria is far from optimal, and far from equitable. Nigeria accounts for half of the deaths from Measles in Africa, the highest prevalence of circulating wild poliovirus in the world, and the country is among the ten countries in the world with vaccine coverage below 50 percent. Studies focusing on community-level determinants therefore have serious policy implications Methods: Multilevel multivariable regression analysis was used on a nationally-representative sample of women aged 15-49 years from the 2003 Nigeria Demographic and Health Survey. Multilevel regression analysis was performed with children (level 1) nested within mothers (level 2), who were in turn nested within communities (level 3). Results: Results show that the pattern of full immunization clusters within families and communities, and that socio-economic characteristics are important in explaining the differentials in full immunization among the children in the study. At the individual level, ethnicity, mothers' occupation, and mothers' household wealth were characteristics of the mothers associated with full immunization of the children. At the community level, the proportion of mothers that had hospital delivery was a determinant of full immunization status. Conclusion: Significant community-level variation remaining after having controlled for child- and mother-level characteristics is indicative of a need for further research on community-levels factors, which would enable extensive tailoring of community-level interventions aimed at improving full immunization and other child health outcomes

Alternative Strategies to Reduce Maternal Mortality in India: A Cost-Effectiveness Analysis

A cost-effectiveness study by Sue Goldie and colleagues finds that better family planning, provision of safe abortion, and improved intrapartum and emergency obstetrical care could reduce maternal mortality in India by 75% in 5 years