Using Qualitative Evidence in Decision Making for Health and Social Interventions: An Approach to Assess Confidence in Findings from Qualitative Evidence Syntheses (GRADE-CERQual)

Published onlineJournal ArticleResearch Support, Non-U.S. Gov'tThis is the final version of the article. Available from Public Library of Science via the DOI in this record.Simon Lewin and colleagues present a methodology for increasing transparency and confidence in qualitative research synthesis.This work was supported by funding from the Department of Reproductive Health and Research, WHO (www.who.int/reproductivehealth/about_us/en/) and Norad (Norwegian Agency for Development Cooperation: www.norad.no) to the Norwegian Knowledge Centre for the Health Services. Additional funding for several of the pilot reviews was provided by the Alliance for Health Policy and Systems Research (www.who.int/alliance-hpsr/en/). We also received funding for elements of this work through the Cochrane supported "Methodological Investigation of Cochrane reviews of Complex Interventions" (MICCI) project (www.cochrane.org). SL is supported by funding from the South African Medical Research Council (www.mrc.ac.za). The funders had no role in study design, data collection and analysis, preparation of the manuscript or the decision to publish

Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age

Background Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P < 1.06 x 10(- 7), of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects

Facilitators and barriers to facility-based delivery in low- and middle-income countries: a qualitative evidence synthesis

High-quality obstetric delivery in a health facility reduces maternal and perinatal morbidity and mortality. This systematic review synthesizes qualitative evidence related to the facilitators and barriers to delivering at health facilities in low- and middle-income countries. We aim to provide a useful framework for better understanding how various factors influence the decision-making process and the ultimate location of delivery at a facility or elsewhere. We conducted a qualitative evidence synthesis using a thematic analysis. Searches were conducted in PubMed, CINAHL and gray literature databases. Study quality was evaluated using the CASP checklist. The confidence in the findings was assessed using the CERQual method. Thirty-four studies from 17 countries were included. Findings were organized under four broad themes: (1) perceptions of pregnancy and childbirth; (2) influence of sociocultural context and care experiences; (3) resource availability and access; (4) perceptions of quality of care. Key barriers to facility-based delivery include traditional and familial influences, distance to the facility, cost of delivery, and low perceived quality of care and fear of discrimination during facility-based delivery. The emphasis placed on increasing facility-based deliveries by public health entities has led women and their families to believe that childbirth has become medicalized and dehumanized. When faced with the prospect of facility birth, women in low- and middle-income countries may fear various undesirable procedures, and may prefer to deliver at home with a traditional birth attendant. Given the abundant reports of disrespectful and abusive obstetric care highlighted by this synthesis, future research should focus on achieving respectful, non-abusive, and high-quality obstetric care for all women. Funding for this project was provided by The United States Agency for International Development (USAID) and the UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research, World Health Organization

A Lie algebra approach to Lie group time integration of constrained systems

peer reviewedLie group integrators preserve by construction the Lie group structure of a nonlinear configuration space. In multibody dynamics, they support a representation of (large) rotations in a Lie group setting that is free of singularities. The resulting equations of motion are differential equations on a manifold with tangent spaces being parametrized by the corresponding Lie algebra. In the present paper, we discuss the time discretization of these equations of motion by a generalized-alpha Lie group integrator for constrained systems and show how to exploit in this context the linear structure of the Lie algebra. This linear structure allows a very natural definition of the generalized-alpha Lie group integrator, an efficient practical implementation and a very detailed error analysis. Furthermore, the Lie algebra approach may be combined with analytical transformations that help to avoid an undesired order reduction phenomenon in generalized-alpha time integration. After a tutorial-like step-by-step introduction to the generalized-alpha Lie group integrator, we investigate its convergence behaviour and develop a novel initialization scheme to achieve second-order accuracy in the application to constrained systems. The theoretical results are illustrated by a comprehensive set of numerical tests for two Lie group formulations of a rotating heavy top