Evidence of association of APOE with age-related macular degeneration: a pooled analysis of 15 studies.

Age-related macular degeneration (AMD) is the most common cause of incurable visual impairment in high-income countries. Previous studies report inconsistent associations between AMD and apolipoprotein E (APOE), a lipid transport protein involved in low-density cholesterol modulation. Potential interaction between APOE and sex, and smoking status has been reported. We present a pooled analysis (n = 21,160) demonstrating associations between late AMD and APOe4 (odds ratio [OR] = 0.72 per haplotype; confidence interval [CI]: 0.65-0.74; P = 4.41×10(-11) ) and APOe2 (OR = 1.83 for homozygote carriers; CI: 1.04-3.23; P = 0.04), following adjustment for age group and sex within each study and smoking status. No evidence of interaction between APOE and sex or smoking was found. Ever smokers had significant increased risk relative to never smokers for both neovascular (OR = 1.54; CI: 1.38-1.72; P = 2.8×10(-15) ) and atrophic (OR = 1.38; CI: 1.18-1.61; P = 3.37×10(-5) ) AMD but not early AMD (OR = 0.94; CI: 0.86-1.03; P = 0.16), implicating smoking as a major contributing factor to disease progression from early signs to the visually disabling late forms. Extended haplotype analysis incorporating rs405509 did not identify additional risks beyond e2 and e4 haplotypes. Our expanded analysis substantially improves our understanding of the association between the APOE locus and AMD. It further provides evidence supporting the role of cholesterol modulation, and low-density cholesterol specifically, in AMD disease etiology.

Sectarian and Nonsectarian Violence: Mothers' Appraisals of Political Conflict in Northern Ireland

Past research on peace and conflict in Northern Ireland has focused on politically motivated violence. However, other types of crime (i.e., nonsectarian) also impact community members. To study the changing nature of violence since the signing of the Belfast Agreement in Northern Ireland, we used a qualitative approach and the Constant Comparative Method to analyze focus group discussions with mothers from segregated Belfast neighborhoods. Participants articulated clear differences between sectarian and nonsectarian violence, and further distinguished sectarian violence along 2 dimensions—overt acts and perceived intergroup threat. Although both sectarian and nonsectarian antisocial behavior related to insecurity, participants described pulling together and increased ingroup social cohesion in response to sectarian incidents. The findings have implications for the study of violence and insecurity as experienced in the everyday lives of mothers, youth, and families in settings of protracted conflict.

Working With Young Children as Co-Researchers: An Approach Informed by the United Nations Convention on the Rights of the Child

Research Findings: Under the United Nations Convention on the Rights of the Child (UNCRC), children have the right to express their views on all matters affecting them and to have those views given due weight. This right applies in the context of research; however, examples of young children being engaged as co-researchers remain rare. Practice or Policy: This article examines the implications of adopting an explicit UNCRC-informed approach to engaging children as co-researchers. It draws on a research project that sought to ascertain young children's views on after-school programs and that involved a university-based research team working along with 2 groups of co-researchers; each composed of 4 children aged 4 to 5. The article discusses the contribution made by children to the development of the research questions and choice of methods and their involvement in the interpretation of the data and dissemination of the findings. It suggests that, although there are limits to what young children can and will want to do in the context of adult-led research studies, an explicit UNCRC-informed approach requires the adoption of supportive strategies that can assist children to engage in a meaningful way, with consequent benefits for the research findings and outputs

Sustained Release of the CCR5 Inhibitors CMPD167 and Maraviroc from Vaginal Rings in Rhesus Macaques

Antiretroviral entry inhibitors are now being considered as vaginally administered microbicide candidates for prevention of sexual transmission of human immunodeficiency virus. Previous studies testing the entry inhibitors maraviroc and CMPD167 in aqueous gel formulations showed efficacy in the macaque challenge model, although protection was highly dependent on the time period between initial gel application and subsequent challenge. In this paper, we describe the sustained release of the entry inhibitors maraviroc and CMPD167 from matrix-type silicone elastomer vaginal rings both in vitro and in vivo. Both inhibitors were released continuously over 28 days from rings in vitro, at rates of 100-2500 µg/day. In 28-day pharmacokinetic studies in rhesus macaques, the compounds were measured in the vaginal fluid and vaginal tissue; steady state fluid concentrations were ~106 fold greater than IC50 values for SHIV-162P3 inhibition in macaque lymphocytes in vitro. Plasma concentrations for both compounds were very low. Pretreatment of macaques with Depo-Provera® (DP), as commonly used in macaque challenge studies, was shown to significantly modify the bio-distribution of the inhibitors, but not the overall amount released. Vaginal fluid and tissue concentrations were significantly decreased while plasma levels increased with DP pretreatment. These observations have implications for designing macaque challenge experiments, and also for ring performance during the human female menstrual cycle. Copyright © 2012, American Society for Microbiology. All Rights Reserved.

Deep sequencing reveals predominant expression of miR-21 amongst the small non-coding RNAs in retinal microvascular endothelial cells

The retinal vascular endothelium is essential for angiogenesis and is involved in maintaining barrier selectivity and vascular tone. The aim of this study was to identify and quantify microRNAs and other small regulatory non-coding RNAs (ncRNAs) which may regulate these crucial functions. Primary bovine retinal microvascular endothelial cells (RMECs) provide a well-characterized in vitro system for studying angiogenesis. RNA extracted from RMECs was used to prepare a small RNA library for deep sequencing (Illumina Genome Analyzer). A total of 6.8 million reads were mapped to 250 known microRNAs in miRBase (release 16). In many cases, the most frequent isomiR differed from the sequence reported in miRBase. In addition, five novel microRNAs, 13 novel bovine orthologs of known human microRNAs and multiple new members of the miR-2284/2285 family were detected. Several similar to 30 nucleotide sno-miRNAs were identified, with the most highly expressed being derived from snoRNA U78. Highly expressed microRNAs previously associated with endothelial cells included miR-126 and miR-378, but the most highly expressed was miR-21, comprising more than one-third of all mapped reads. Inhibition of miR-21 with an LNA inhibitor significantly reduced proliferation, migration, and tube-forming capacity of RMECs. The independence from prior sequence knowledge provided by deep sequencing facilitates analysis of novel microRNAs and other small RNAs. This approach also enables quantitative evaluation of microRNA expression, which has highlighted the predominance of a small number of microRNAs in RMECs. Knockdown of miR-21 suggests a role for this microRNA in regulation of angiogenesis in the retinal microvasculature. J. Cell. Biochem. 113: 20982111, 2012. (C) 2012 Wiley Periodicals, Inc.

Children’s perceptions of primary science assessment in England and Wales

This study builds on and contributes to work on assessment of children in primary school, particularly in science. Previous research has examined primary science assessment from different standpoints, but no studies have speci?cally addressed children’s perspectives. This article provides additional insight into issues surrounding children’s assessment in primary school and how the assessment of science might develop in England after the science SATs (Standard Assessment Tests) were abolished in 2009. Some research suggests that primary science assessment via SATs is a major reason for the observed decline in children’s engagement with science in upper primary and lower secondary school. The analytic focus on engaging children as coresearchers to assist in the process of gathering informed views and interpreting ?ndings from a large sample of children’s views enables another contribution. The study, based on a survey of 1000 children in primary and secondary schools in England and Wales, reveals that despite being assessed under two different regimes (high-stakes national tests in England and moderated teacher assessment in Wales), children’s views of science assessment are remarkably consistent. Most appreciate the usefulness of science assessment and value frequent, non-SATs testing for monitoring/improving science progress. There was a largely negative impact, however, of science
assessment on children’s well-being, particularly due to stress. The paper demonstrates that children provide an important perspective on assessment and that including their views can improve policy-making in relation to primary science assessment.

Children’s rights and research processes: Assisting children to (in)formed views

Acknowledging children as rights-holders has significant implications for research processes. What is distinctive about a children’s rights informed approach to research is a focus not only on safe, inclusive and engaging opportunities for children to express their views but also on deliberate strategies to assist children in the formation of their views. The article reflects on a body of work with children as co-researchers and as participants and demonstrates that building capacity on the substantive research issues enables children to contribute more confidently. It concludes with a conceptualization of this approach integrating relevant international children’s rights standards.

Glacial Survival of Boreal Trees in Northern Scandinavia

It is commonly believed that trees were absent in Scandinavia during the last glaciation and first recolonized the Scandinavian Peninsula with the retreat of its ice sheet some 9000 years ago. Here, we show the presence of a rare mitochondrial DNA haplotype of spruce that appears unique to Scandinavia and with its highest frequency to the west—an area believed to sustain ice-free refugia during most of the last ice age. We further show the survival of DNA from this haplotype in lake sediments and pollen of Trøndelag in central Norway dating back ~10,300 years and chloroplast DNA of pine and spruce in lake sediments adjacent to the ice-free Andøya refugium in northwestern Norway as early as ~22,000 and 17,700 years ago, respectively. Our findings imply that conifer trees survived in ice-free refugia of Scandinavia during the last glaciation, challenging current views on survival and spread of trees as a response to climate changes.

Activating optomechanical entanglement

We propose an optomechanical setup where the activation of entanglement through the pre-availability of non-classical correlations can be demonstrated experimentally. We analyse the conditions under which the scheme is successful and relate them to the current experimental state of the art. The successful activation of entanglement embodies an interesting alternative to current settings for the revelation of fully mechanical nonclassicality.

Global Quantum Correlation in the Ising model

We study quantum correlations in an isotropic Ising ring under the effects of a transverse magnetic field. After characterizing the behavior of two-spin quantum correlations, we extend our analysis to global properties of the ring, using a figure of merit for quantum correlations that shows enough sensitivity to reveal the drastic changes in the properties of the system at criticality. This opens up the possibility to relate statistical properties of quantum many-body systems to suitably tailored measures of quantum correlations that capture features going far beyond standard quantum entanglement.