Partitioning Heritability of Regulatory and Cell-Type-Specific Variants across 11 Common Diseases

Regulatory and coding variants are known to be enriched with associations identified by genome-wide association studies (GWASs) of complex disease, but their contributions to trait heritability are currently unknown. We applied variance-component methods to imputed genotype data for 11 common diseases to partition the heritability explained by genotyped SNPs () across functional categories (while accounting for shared variance due to linkage disequilibrium). Extensive simulations showed that in contrast to current estimates from GWAS summary statistics, the variance-component approach partitions heritability accurately under a wide range of complex-disease architectures. Across the 11 diseases DNaseI hypersensitivity sites (DHSs) from 217 cell types spanned 16% of imputed SNPs (and 24% of genotyped SNPs) but explained an average of 79% (SE = 8%) of  from imputed SNPs (5.1× enrichment; p = 3.7 × 10⁻¹⁷) and 38% (SE = 4%) of  from genotyped SNPs (1.6× enrichment, p = 1.0 × 10⁻⁴). Further enrichment was observed at enhancer DHSs and cell-type-specific DHSs. In contrast, coding variants, which span 1% of the genome, explained <10% of  despite having the highest enrichment. We replicated these findings but found no significant contribution from rare coding variants in independent schizophrenia cohorts genotyped on GWAS and exome chips. Our results highlight the value of analyzing components of heritability to unravel the functional architecture of common disease.

Care Planning in Children and Young Peoples Nursing

Care Planning in Children and Young People's Nursing addresses a selection of the most common concerns that arise when planning care for infants, children and young people within the hospital and community setting. Clear and detailed, this text reflects both the uniqueness and diversity of contemporary children's nursing and utilizes images and case studies to provide a holistic insight into the practice of care planning through the reporting of best available evidence and current research, policy and education.

Divided into sections for ease of reference, Care Planning in Children and Young People’s Nursing explores both the theory and practice of care planning. Chapters on the principles of care planning include issues such as managing risk, safeguarding children, ethical and legal implications, integrated care pathways, interprofessional assessment, and invaluable parent perspectives. Additional chapters on the application of planning care examine the practical aspects of a wide range of specific conditions including cystic fibrosis, obesity, cardiac/renal failure and HIV/AIDS. Each chapter is interactive, with questions, learning activities and points for discussion creating an engaging and enquiry-based learning approach.

Care Planning in Children and Young People’s Nursing is a definitive resource, reflecting innovative practice which is suitable for undergraduate and postgraduate nurse education.

Reductive photocatalysis and smart inks

Semiconductor-sensitised photocatalysis is a well-established and growing area of research, innovation and commercialisation; the latter being mostly limited to the use of TiO2 as the semiconductor. Most of the work on semiconductor photocatalytic systems uses oxygen as the electron acceptor and explores a wide range of electron donors; such systems can be considered to be examples of oxidative photocatalysis, OP. OP underpins most current examples of commercial self-cleaning materials, such as: glass, tiles, concrete, paint and fabrics. OP, and its myriad of applications, have been reviewed extensively over the years both in this journal and elsewhere. However, the ability of TiO2, and other semiconductor sensitisers, to promote reductive photocatalysis, RP, especially of dyes, is significant and, although less well-known, is of growing importance. In such systems, the source of the electrons is some easily oxidised species, such as glycerol. One recent, significant example of a RP process is with respect to photocatalyst activity indicator inks. paiis, which provide a measure of the activity of a photocatalytic film under test via the rate of change of colour of the dye in the ink coating due to irreversible RP. In contrast, by incorporating the semiconductor sensitiser in the ink, rather than outside it, it is possible to create an effective UV dosimeter, based on RP, which can be used as a sun-burn warning indicator. In the above examples the dye is reduced irreversibly, but when the photocatalyst in an ink is used to reversibly photoreduce a dye, a novel, colourimetric oxygen-sensitive indicator ink can be created, which has commercial potential in the food packaging industry. Finally, if no dye is present in the ink, and the semiconductor photocatalyst-loaded ink film coats an easily reduced substrate, such as a metal oxide film, then it can be used to reduce the latter and so, for example, clean up tarnished steel. The above are examples of smart inks, i.e. inks that are active and provide either dynamic information (such as UV dose or O2 level) or a useful function (such as tarnish removal), and all work via a RP process and are reviewed here

A sting in the spit: widespread cross-infection of multiple RNA viruses across wild and managed bees

Declining populations of bee pollinators are a cause of concern, with major repercussions for biodiversity loss and food security. RNA viruses associated with honeybees represent a potential threat to other insect pollinators, but the extent of this threat is poorly understood. This study aims to attain a detailed understanding of the current and ongoing risk of emerging infectious disease (EID) transmission between managed and wild pollinator species across a wide range of RNA viruses. Within a structured large-scale national survey across 26 independent sites, we quantify the prevalence and pathogen loads of multiple RNA viruses in co-occurring managed honeybee (Apis mellifera) and wild bumblebee (Bombus spp.) populations. We then construct models that compare virus prevalence between wild and managed pollinators. Multiple RNA viruses associated with honeybees are widespread in sympatric wild bumblebee populations. Virus prevalence in honeybees is a significant predictor of virus prevalence in bumblebees, but we remain cautious in speculating over the principle direction of pathogen transmission. We demonstrate species-specific differences in prevalence, indicating significant variation in disease susceptibility or tolerance. Pathogen loads within individual bumblebees may be high and in the case of at least one RNA virus, prevalence is higher in wild bumblebees than in managed honeybee populations. Our findings indicate widespread transmission of RNA viruses between managed and wild bee pollinators, pointing to an interconnected network of potential disease pressures within and among pollinator species. In the context of the biodiversity crisis, our study emphasizes the importance of targeting a wide range of pathogens and defining host associations when considering potential drivers of population decline.

The Day After Tomorrow: Transition Management, Spatial Planning & the Low Carbon Economy

Many of the societal challenges that current spatial planning practice claims to be addressing (climate change, peak oil, obesity, aging society etc) encompass issues and timescales that lie beyond the traditional scope planning policy (Campbell 2006). The example of achieving a low carbon economy typifies this in that it demands a process of society-wide transition, involving steering a wide range of factors (markets, infrastructure, governance, individual behaviour etc). Such a process offers a challenge to traditional approaches to planning as they cannot be guided by a fixed blueprint, given the timescales involved (up to 50 years) and an enhanced level of uncertainty, social resistance, lack of control over implementation and a danger of ‘policy lock in’ (Kemp et al 2007). One approach to responding to these challenges is the concept of transition management which has emerged from studies of science, technology and innovation (Geels 2002, Markard et al 2012). Although not without criticism, this perspective attempts to uncertainty and complexity encompassing long term visions that integrates multi-level, multi-actor and multi-domain perspectives (Rotmans et al 2001).
 
Given its origins, research on transition management has tended to neglect spatial contexts (Coenen et al 2012) and, related to this, it’s relationship with spatial planning is poorly understood. Using the example of the low carbon transition, this paper will review the relationships between the concepts, methodologies and goals of transition management and spatial planning to explore whether a closer integration of the two fields offers benefits to achieving the long term challenges facing society.
 

Atmospheric Pressure DC Plasma Processing of TIO2/PEDOT:PSS Nanocomposites

In this work we demonstrate the synthesis of a TiO2/PEDOT:PSS nanocomposite material in aqueous solution through atmospheric pressure direct current (DC) plasma processing at room temperature. The dispersion of the TiO2 nanoparticles is enhanced after microplasma processing, and TiO2/polymer hybrid nanoparticles with a distinct core shell structure have been obtained. We have observed increased TiO2/PEDOT:PSS nanocomposite electrical conductivity due to microplasma processing. The improvement in nanocomposite properties is due to the enhanced dispersion and stability in liquid polymer of microplasma treated TiO2 nanoparticles. Both plasma induced surface charge and nanoparticle surface termination with specific plasma chemical species are thought to provide an enhanced barrier to nanoparticle agglomeration and promote nanoparticle-polymer bonding, which is expected to have a significant benefit in materials processing with inorganic nanoparticles for wide range of applications.

Artificial neural network model to predict compositional viscosity over a broad range of temperatures

The objective of this study is to provide an alternative model approach, i.e., artificial neural network (ANN) model, to predict the compositional viscosity of binary mixtures of room temperature ionic liquids (in short as ILs) [C _n-mim] [NTf ₂] with n=4, 6, 8, 10 in methanol and ethanol over the entire range of molar fraction at a broad range of temperatures from T=293.0328.0K. The results show that the proposed ANN model provides alternative way to predict compositional viscosity successfully with highly improved accuracy and also show its potential to be extensively utilized to predict compositional viscosity over a wide range of temperatures and more complex viscosity compositions, i.e., more complex intermolecular interactions between components in which it would be hard or impossible to establish the analytical model. © 2010 IEEE.

Incorporation of spiritual care as a component of healthcare and medical education: comparison of viewpoints of healthcare providers from a rural community hospital in Uganda with those of medical students from United Kingdrom

This study addresses cultural differences regarding views on the place for spirituality within healthcare training and delivery. A questionnaire was devised using a 5-point ordinal scale, with additional free text comments assessed by thematic analysis, to compare the views of Ugandan healthcare staff and students with those of (1) visiting international colleagues at the same hospital; (2) medical faculty and students in United Kingdom. Ugandan healthcare personnel were more favourably disposed towards addressing spiritual issues, their incorporation within compulsory healthcare training, and were more willing to contribute themselves to delivery than their European counterparts. Those from a nursing background also attached a greater importance to spiritual health and provision of spiritual care than their medical colleagues. Although those from a medical background recognised that a patient’s religiosity and spirituality can affect their response to their diagnosis and prognosis, they were more reticent to become directly involved in provision of such care, preferring to delegate this to others with greater expertise. Thus, differences in background, culture and healthcare organisation are important, and indicate that the wide range of views expressed in the current literature, the majority of which has originated in North America, are not necessarily transferable between locations; assessment of these issues locally may be the best way to plan such training and incorporation of spiritual care into clinical practice.

Host Defence Peptide LL-37; Effects of truncation on antimicrobial activity

Background: The oral cavity is an ideal environment for colonisation by micro-organisms. A first line of defence against microbial infection is the secretion of broad spectrum host defence peptides (HDPs). In the current climate of antibiotic resistance, exploiting naturally occurring HDPs or synthetic derivatives (mimetics) to combat infection is particularly appealing. The human cathelicidin, LL-37 is one such HDP expressed ubiquitously by epithelial cells and neutrophils. LL-37 exhibits the ability to bind lipopolysaccharide (LPS) and displays broad spectrum activity against a wide range of bacteria. The current study focuses on truncation of LL-37 and defining the antimicrobial and LPS binding activity of the resultant mimetics. Objectives: To assess the antimicrobial and LPS binding activity of LL-37 and three truncated mimetics (KE-18, EF-14 and KR-12). Methods: Peptides were synthesised in-house by Fmoc solid phase peptide synthesis or obtained commercially. Antimicrobial activity was determined using a radial diffusion assay and ability to bind LPS was determined by indirect ELISA. Results: LL-37 and mimetics displayed antimicrobial activity against Streptococcus mutans and Enterococcus Faecalis. KE-18 and KR-12 were shown to possess antimicrobial activity against both pathogens whereas EF-14 was the least antimicrobial. In terms of LPS binding, KE-18 and KR-12 were both effective whereas EF-14 showed the least activity of the three mimetics. Conclusion: Truncation of LL-37 can yield peptides which retain antimicrobial activities and have the ability to bind LPS. Interestingly in some cases the truncation of LL-37 produced mimetics with greater potency than the parent molecule in terms of antimicrobial activity and LPS binding. This work was funded by DEL and the Diabetes Wellness Foundation.

LaGomiCs - Lagomorph Genomics Consortium: An International Collaborative Effort for Sequencing the Genomes of an Entire Mammalian Order

The order Lagomorpha comprises about 90 living species, divided in 2 families: the pikas (Family Ochotonidae), and the rabbits, hares, and jackrabbits (Family Leporidae). Lagomorphs are important economically and scientifically as major human food resources, valued game species, pests of agricultural significance, model laboratory animals, and key elements in food webs. A quarter of the lagomorph species are listed as threatened. They are native to all continents except Antarctica, and occur up to 5000 m above sea level, from the equator to the Arctic, spanning a wide range of environmental conditions. The order has notable taxonomic problems presenting significant difficulties for defining a species due to broad phenotypic variation, overlap of morphological characteristics, and relatively recent speciation events. At present, only the genomes of 2 species, the European rabbit (Oryctolagus cuniculus) and American pika (Ochotona princeps) have been sequenced and assembled. Starting from a paucity of genome information, the main scientific aim of the Lagomorph Genomics Consortium (LaGomiCs), born from a cooperative initiative of the European COST Action “A Collaborative European Network on Rabbit Genome Biology—RGB-Net” and the World Lagomorph Society (WLS), is to provide an international framework for the sequencing of the genome of all extant and selected extinct lagomorphs. Sequencing the genomes of an entire order will provide a large amount of information to address biological problems not only related to lagomorphs but also to all mammals. We present current and planned sequencing programs and outline the final objective of LaGomiCs possible through broad international collaboration.

Roadmap to clinical use of gold nanoparticles for radiation sensitization

The past decade has seen a dramatic increase in interest in the use of gold nanoparticles (GNPs) as radiation sensitizers for radiation therapy. This interest was initially driven by their strong absorption of ionizing radiation and the resulting ability to increase dose deposited within target volumes even at relatively low concentrations. These early observations are supported by extensive experimental validation, showing GNPs' efficacy at sensitizing tumors in both in vitro and in vivo systems to a range of types of ionizing radiation, including kilovoltage and megavoltage X rays as well as charged particles. Despite this experimental validation, there has been limited translation of GNP-mediated radiation sensitization to a clinical setting. One of the key challenges in this area is the wide range of experimental systems that have been investigated, spanning a range of particle sizes, shapes, and preparations. As a result, mechanisms of uptake and radiation sensitization have remained difficult to clearly identify. This has proven a significant impediment to the identification of optimal GNP formulations which strike a balance among their radiation sensitizing properties, their specificity to the tumors, their biocompatibility, and their imageability in vivo. This white paper reviews the current state of knowledge in each of the areas concerning the use of GNPs as radiosensitizers, and outlines the steps which will be required to advance GNP-enhanced radiation therapy from their current pre-clinical setting to clinical trials and eventual routine usage.

Investigation of the effects of flow conditions at rotor inlet on mixed flow turbine performance for automotive applications

Current trends in the automotive industry have placed increased importance on engine downsizing for passenger vehicles. Engine downsizing often results in reduced power output and turbochargers have been relied upon to restore the power output and maintain drivability. As improved power output is required across a wide range of engine operating conditions, it is necessary for the turbocharger to operate effectively at both design and off-design conditions. One off-design condition of considerable importance for turbocharger turbines is low velocity ratio operation, which refers to the combination of high exhaust gas velocity and low turbine rotational speed. Conventional radial flow turbines are constrained to achieve peak efficiency at the relatively high velocity ratio of 0.7, due the requirement to maintain a zero inlet blade angle for structural reasons. Several methods exist to potentially shift turbine peak efficiency to lower velocity ratios. One method is to utilize a mixed flow turbine as an alternative to a radial flow turbine. In addition to radial and circumferential components, the flow entering a mixed flow turbine also has an axial component. This allows the flow to experience a non-zero inlet blade angle, potentially shifting peak efficiency to a lower velocity ratio when compared to an equivalent radial flow turbine.
This study examined the effects of varying the flow conditions at the inlet to a mixed flow turbine and evaluated the subsequent impact on performance. The primary parameters examined were average inlet flow angle, the spanwise distribution of flow angle across the inlet and inlet flow cone angle. The results have indicated that the inlet flow angle significantly influenced the degree of reaction across the rotor and the turbine efficiency. The rotor studied was a custom in-house design based on a state-of-the-art radial flow turbine design. A numerical approach was used as the basis for this investigation and the numerical model has been validated against experimental data obtained from the cold flow turbine test rig at Queen’s University Belfast. The results of the study have provided a useful insight into how the flow conditions at rotor inlet influence the performance of a mixed flow turbine.