Measuring attitude towards Buddhism and Sikhism : internal consistency reliability for two new instruments

This paper describes and discusses the development and empirical properties of two new 24-item scales – one measuring attitude toward Buddhism and the other measuring attitude toward Sikhism. The scale is designed to facilitate inter-faith comparisons within the psychology of religion alongside the well-established Francis Scale of Attitude toward Christianity. Data were obtained from a multi-religious sample of 369 school pupils aged between 13 and 15 in London. Application of the two scales demonstrated that adolescents had a more positive attitude to Buddhism than Sikhism. The findings confirm the reliability of the scales and commend them for further use

Understanding pregnancy planning in a low-income country setting: validation of the London measure of unplanned pregnancy in Malawi

This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: The London Measure of Unplanned Pregnancy (LMUP) is a new and psychometrically valid measure of pregnancy intention that was developed in the United Kingdom. An improved understanding of pregnancy intention in low-income countries, where unintended pregnancies are common and maternal and neonatal deaths are high, is necessary to inform policies to address the unmet need for family planning. To this end this research aimed to validate the LMUP for use in the Chichewa language in Malawi.Methods: Three Chichewa speakers translated the LMUP and one translation was agreed which was back-translated and pre-tested on five pregnant women using cognitive interviews. The measure was field tested with pregnant women who were recruited at antenatal clinics and data were analysed using classical test theory and hypothesis testing.Results: 125 women aged 15-43 (median 23), with parities of 1-8 (median 2) completed the Chichewa LMUP. There were no missing data. The full range of LMUP scores was captured. In terms of reliability, the scale was internally consistent (Cronbach's alpha = 0.78) and test-retest data from 70 women showed good stability (weighted Kappa 0.80). In terms of validity, hypothesis testing confirmed that unmarried women (p = 0.003), women who had four or more children alive (p = 0.0051) and women who were below 20 or over 29 (p = 0.0115) were all more likely to have unintended pregnancies. Principal component analysis showed that five of the six items loaded onto one factor, with a further item borderline. A sensitivity analysis to assess the effect of the removal of the weakest item of the scale showed slightly improved performance but as the LMUP was not significantly adversely affected by its inclusion we recommend retaining the six-item score.Conclusion: The Chichewa LMUP is a valid and reliable measure of pregnancy intention in Malawi and can now be used in research and/or surveillance. This is the first validation of this tool in a low-income country, helping to demonstrate that the concept of pregnancy planning is applicable in such a setting. Use of the Chichewa LMUP can enhance our understanding of pregnancy intention in Malawi, giving insight into the family planning services that are required to better meet women's needs and save lives. © 2013 Hall et al.; licensee BioMed Central Ltd.Dr Hall’s Wellcome Trust Research Training Fellowship, grant number 097268/Z/11/Z

Nanoemulsion Adjuvant Augments Retinaldehyde Dehydrogenase Activity in Dendritic Cells via MyD88 Pathway

Mucosal surfaces are the primary point of entry for many infectious agents and mucosal immune responses serve as the primary defense to these pathogens. In order to mount an effective mucosal immune response, it is important to induce T cell homing to mucosal surfaces. Conventional vaccine adjuvants induce strong systemic immunity but often fail to produce mucosal immunity. We have developed an oil-in-water nanoemulsion (NE) adjuvant that provides mucosal immunity and efficient protection against mucosal pathogens when administered as part of an intranasal vaccine. In the present study, we demonstrate that intranasal immunization with NE indirectly activates the retinaldehyde dehydrogenase (RALDH) activity in dendritic cells through epithelial cell activity leading to SIgA as well as potent cellular responses and expression of α4β7 and CCR9 gut homing receptors on T cells. Confirming these findings, ex-vivo stimulation of splenocytes from NE nasally immunized animals showed increase in Th1/Th17 cytokines while suppressing Th2 responses. In examining mechanisms underlying this activation NE activated RALDH via MyD88 dependent pathways in DCs but did not activate the retinoic acid receptor directly. These results suggest that RALDH immune activities can be achieved by epithelial activation without direct RAR activation, which has significant implications for understanding mucosal immunity and the design of mucosal vaccines

The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial

BRAF genomic alterations are the most common oncogenic drivers in pediatric low-grade glioma (pLGG). Arm 1 (n = 77) of the ongoing phase 2 FIREFLY-1 (PNOC026) trial investigated the efficacy of the oral, selective, central nervous system-penetrant, type II RAF inhibitor tovorafenib (420 mg m$^{-}$$^{2}$ once weekly; 600 mg maximum) in patients with BRAF-altered, relapsed/refractory pLGG. Arm 2 (n = 60) is an extension cohort, which provided treatment access for patients with RAF-altered pLGG after arm 1 closure. Based on independent review, according to Response Assessment in Neuro-Oncology High-Grade Glioma (RANO-HGG) criteria, the overall response rate (ORR) of 67% met the arm 1 prespecified primary endpoint; median duration of response (DOR) was 16.6 months; and median time to response (TTR) was 3.0 months (secondary endpoints). Other select arm 1 secondary endpoints included ORR, DOR and TTR as assessed by Response Assessment in Pediatric Neuro-Oncology Low-Grade Glioma (RAPNO) criteria and safety (assessed in all treated patients and the primary endpoint for arm 2, n = 137). The ORR according to RAPNO criteria (including minor responses) was 51%; median DOR was 13.8 months; and median TTR was 5.3 months. The most common treatment-related adverse events (TRAEs) were hair color changes (76%), elevated creatine phosphokinase (56%) and anemia (49%). Grade ≥3 TRAEs occurred in 42% of patients. Nine (7%) patients had TRAEs leading to discontinuation of tovorafenib. These data indicate that tovorafenib could be an effective therapy for BRAF-altered, relapsed/refractory pLGG. ClinicalTrials.gov registration: NCT04775485

Coassembled nanostructured bioscaffold reduces the expression of proinflammatory cytokines to induce apoptosis in epithelial cancer cells

The local inflammatory environment of the cell promotes the growth of epithelial cancers. Therefore, controlling inflammation locally using a material in a sustained, non-steroidal fashion can effectively kill malignant cells without significant damage to surrounding healthy cells. A promising class of materials for such applications is the nanostructured scaffolds formed by epitope presenting minimalist self-assembled peptides; these are bioactive on a cellular length scale, while presenting as an easily handled hydrogel. Here, we show that the assembly process can distribute an anti-inflammatory polysaccharide, fucoidan, localized to the nanofibers within the scaffold to create a biomaterial for cancer therapy. We show that it supports healthy cells, while inducing apoptosis in cancerous epithelial cells, as demonstrated by the significant down-regulation of gene and protein expression pathways associated with epithelial cancer progression. Our findings highlight an innovative material approach with potential applications in local epithelial cancer immunotherapy and drug delivery

Taking the Metabolic Pulse of the World\u27s Coral Reefs

Worldwide, coral reef ecosystems are experiencing increasing pressure from a variety of anthropogenic perturbations including ocean warming and acidification, increased sedimentation, eutrophication, and overfishing, which could shift reefs to a condition of net calcium carbonate (CaCO3) dissolution and erosion. Herein, we determine the net calcification potential and the relative balance of net organic carbon metabolism (net community production; NCP) and net inorganic carbon metabolism (net community calcification; NCC) within 23 coral reef locations across the globe. In light of these results, we consider the suitability of using these two metrics developed from total alkalinity (TA) and dissolved inorganic carbon (DIC) measurements collected on different spatiotemporal scales to monitor coral reef biogeochemistry under anthropogenic change. All reefs in this study were net calcifying for the majority of observations as inferred from alkalinity depletion relative to offshore, although occasional observations of net dissolution occurred at most locations. However, reefs with lower net calcification potential (i.e., lower TA depletion) could shift towards net dissolution sooner than reefs with a higher potential. The percent influence of organic carbon fluxes on total changes in dissolved inorganic carbon (DIC) (i.e., NCP compared to the sum of NCP and NCC) ranged from 32% to 88% and reflected inherent biogeochemical differences between reefs. Reefs with the largest relative percentage of NCP experienced the largest variability in seawater pH for a given change in DIC, which is directly related to the reefs ability to elevate or suppress local pH relative to the open ocean. This work highlights the value of measuring coral reef carbonate chemistry when evaluating their susceptibility to ongoing global environmental change and offers a baseline from which to guide future conservation efforts aimed at preserving these valuable ecosystems

De novo mutations in histone modifying genes in congenital heart disease

Congenital heart disease (CHD) is the most frequent birth defect, affecting 0.8% of live births1. Many cases occur sporadically and impair reproductive fitness, suggesting a role for de novo mutations. By analysis of exome sequencing of parent-offspring trios, we compared the incidence of de novo mutations in 362 severe CHD cases and 264 controls. CHD cases showed a significant excess of protein-altering de novo mutations in genes expressed in the developing heart, with an odds ratio of 7.5 for damaging mutations. Similar odds ratios were seen across major classes of severe CHD. We found a marked excess of de novo mutations in genes involved in production, removal or reading of H3K4 methylation (H3K4me), or ubiquitination of H2BK120, which is required for H3K4 methylation2–4. There were also two de novo mutations in SMAD2; SMAD2 signaling in the embryonic left-right organizer induces demethylation of H3K27me5. H3K4me and H3K27me mark `poised' promoters and enhancers that regulate expression of key developmental genes6. These findings implicate de novo point mutations in several hundred genes that collectively contribute to ~10% of severe CHD