A children's nurse's role in the global development of a child with diabetes mellitus.

The nursing care of a six year old with type 1 diabetes reveals the importance of accurate control of the condition for normal physical, emotional and cognitive development. Clearly the children's nurse can educate and support the child, parents and extended family towards achieving independence and self-care. Theoretical knowledge of normal child maturation can guide nurses to constantly adapt their modes of communication and nursing skills, so as to promote every aspect and stage of the child's growth. Prevalence of type 1 diabetes is increasing, and nurses should use their close professional involvement with patients to assist research at every opportunity.

Characterisation of a novel panel of polymorphic microsatellite loci for the liver fluke, Fasciola hepatica, using a next generation sequencing approach

The liver fluke, Fasciola hepatica is an economically important pathogen of sheep and cattle and has been described by the WHO as a re-emerging zoonosis. Control is heavily reliant on the use of drugs, particularly triclabendazole and as a result resistance has now emerged. The population structure of F. hepatica is not well known, yet it can impact on host-parasite interactions and parasite control with drugs, particularly regarding the spread of triclabendazole resistance. We have identified 2448 potential microsatellites from 83Mb of F. hepatica genome sequence using msatfinder. Thirty-five loci were developed and optimised for microsatellite PCR, resulting in a panel of 15 polymorphic loci, with a range of three to 15 alleles. This panel was validated on genomic DNA from 46 adult F. hepatica; 38 liver flukes sourced from a Northwest abattoir, UK and 8 liver flukes from an established isolate (Shrewsbury; Ridgeway Research). Evidence for null alleles was found at four loci (Fh_1, Fh_8, Fh_13 and Fh_14), which showed markedly higher levels of homozygosity than the remaining 11 loci. Of the 38 liver flukes isolated from cattle livers (n=10) at the abattoir, 37 genotypes were identified. Using a multiplex approach all 15 loci could be amplified from several life cycle stages that typically yield low amounts of DNA, including metacercariae, the infective life cycle stage present on pasture, highlighting the utility of this multiplex microsatellite panel. This study reports the largest panel of microsatellite markers available to date for population studies of F. hepatica and the first multiplex panel of microsatellite markers that can be used for several life cycle stages.

An analysis of stage performance in automotive turbocharger centrifugal compressors

As the concept of engine downsizing becomes ever more integrated into automotive powertrain development strategies, so too does the pressure on turbocharger manufacturers to deliver improvements in map width and a reduction in the mass flow rate at which compressor surge occurs. A consequence of this development is the increasing importance of recirculating flows, both in the impeller inlet and outlet domains, on stage performance.
The current study seeks to evaluate the impact of the inclusion of impeller inlet recirculation on a meanline centrifugal compressor design tool. Using a combination of extensive test data, single passage CFD predictions, and 1-D analysis it is demonstrated how the addition of inlet recirculation modelling impacts upon stage performance close to the surge line. It is also demonstrated that, in its current configuration, the accuracy of the 1-D model prediction diminishes significantly with increasing blade tip speed.
Having ascertained that the existing model requires further work, an evaluation of the vaneless diffuser modelling method currently employed within the existing 1-D model is undertaken. The comparison of the predicted static pressure recovery coefficient with test data demonstrated the inherent inadequacies in the resulting prediction, in terms of both magnitude and variation with flow rate. A simplified alternative method based on an equivalent friction coefficient is also presented that, with further development, could provide a significantly improved stage performance prediction.

A review of offshore wind power development in the United Kingdom

Currently wind power is dominated by onshore wind farms. However, as the demand for power grows driven by security of energy supply issues, dwindling fossil fuel supplies and greenhouse gas emissions reduction targets, offshore wind power will develop rapidly because of the decline of viable onshore sites. The United Kingdom has a target of 21% renewable electricity by 2020 and this is expected to come mostly from wind power. Britain is the most active internationally in terms of offshore wind farm development with almost 48GW in some stage of development. In addition the Scottish Government, the Northern Ireland Executive and the Government of Ireland undertook the 'Irish-Scottish Links on Energy Study' (ISLES), which examined the feasibility of creating an offshore interconnected transmission network and subsea electricity grid based on renewable energy sources off the coast of western Scotland and the Irish Sea. The aim of this paper is to provide an appraisal of offshore wind power development with a focus on the United Kingdom. © 2013 IEEE.

Prostaglandin E2 as a regulator of germ cells during ovarian development

CONTEXT: The formation of primordial follicles occurs during fetal life yet is critical to the determination of adult female fertility. Prior to this stage, germ cells proliferate, enter meiosis, and associate with somatic cells. Growth and survival factors implicated in these processes include activin A (INHBA), the neurotrophins BDNF and NT4 (NTF5), and MCL1. The prostaglandins have pleiotrophic roles in reproduction, notably in ovulation and implantation, but there are no data regarding roles for prostaglandins in human fetal ovarian development.

OBJECTIVE: The aim of the study was to investigate a possible role for prostaglandin (PG) E(2) in human fetal ovary development.

DESIGN: In vitro analysis of ovarian development between 8 and 20 wk gestation was performed.

MAIN OUTCOME MEASURE(S): The expression patterns of PG synthesis enzymes and the PGE(2) receptors EP2 and EP4 in the ovary were assessed, and downstream effects of PGE(2) on gene expression were analyzed.

RESULTS: Ovarian germ cells express the PG synthetic enzymes COX2 and PTGES as well as the EP2 and EP4 receptors, whereas COX1 is expressed by ovarian somatic cells. Treatment in vitro with PGE(2) increased the expression of BDNF mRNA 1.7 +/- 0.16-fold (P = 0.004); INHBA mRNA, 2.1 +/- 0.51-fold (P = 0.04); and MCL1 mRNA, 1.15 +/- 0.06-fold (P = 0.04), but not that of OCT4, DAZL, VASA, NTF5, or SMAD3.

CONCLUSIONS: These data indicate novel roles for PGE(2) in the regulation of germ cell development in the human ovary and show that these effects may be mediated by the regulation of factors including BDNF, activin A, and MCL1.

Larval development of the pedunculate barnacles Octolasmis angulata Aurivillius 1894 and Octolasmis cor Aurivillius 1892 (Cirripedia: Thoracica: Poecilasmatidae) from the gills of the mud crab, Scylla tranquebarica Fabricius, 1798

Detailed studies of larval development of Octolasmis angulata and Octolasmis cor are pivotal in understanding the larval morphological evolution as well as enhancing the functional ecology. Six planktotrophic naupliar stages and one non-feeding cyprid stage are documented in details for the first time for the two species of Octolasmis. Morphologically, the larvae of O. angulata and O. cor are similar in body size, setation patterns on the naupliar appendages, labrum, dorsal setae-pores, frontal horns, cyprid carapace, fronto-lateral gland pores, and lattice organs. Numbers of peculiarities were observed on the gnathobases of the antennae and mandible throughout the naupliar life-cycle. The setation pattern on the naupliar appendages are classified based on the segmentation on the naupliar appendages. The nauplius VI of both species undergoes a conspicuous change before metamorphosis into cyprid stage. The cyprid structures begin to form and modify beneath the naupliar body towards the end of stage VI. This study emphasises the importance of the pedunculate barnacle larval developmental studies not only to comprehend the larval morphological evolution but also to fill in the gaps in understanding the modification of the naupliar structures to adapt into the cyprid life-style.

Carbon distribution within the plant and rhizosphere in laboratory and field-grown Lolium perenne at different stages of development

Carbon distribution within perennial ryegrass was determined at different stages of plant development, by pulse-labelling laboratory and field-grown plants with ¹⁴C-CO₂. During the early stages of growth (23-51 days), C distribution of laboratory grown plants was not markedly affected by plant age, with 12.4-24% of net assimilated label lost into the soil as root-soil respiration. The percentage of net assimilate translocated below ground was 20-28% during this stage of growth. At 65 days, the percentage of the label translocated below ground decreased to 8.1% of the net assimilate, with a subsequent decrease in root-soil respiration to 3.9%. The ability of the plant to fix the label (expressed in MBq g^-1 oven dry total plant weight) decreased steadily as the plants aged. When the 30 day old plants were subjected to water stress (soil water potential -1.5 MPa) for 2 days before pulse-labelling, root-soil respiration of the pulse-label decreased compared with plants grown at field capacity. The distribution of a ¹⁴C pulse-label within perennial ryegrass grown under field conditions was found to be dependent on the age of the plants. For 4 week old plants, 67% of net assimilated label was translocated below ground, with 64.8% of this respired by the roots and soil. Less label was translocated below ground at subsequent pulse-labels from weeks 8 to 24. The proportion of label translocated below ground respired by the roots and soil also decreased. The investment of label in the plant shoots was found to be greater in field grown plants as compared to plants of the same age grown in a controlled, laboratory environment. © 1990.

Environmental and social supply chain management sustainability practices: construct development and measurement

The purpose of this paper is to conceptualise and operationalise the concept of supply chain management sustainability practices. Based on a multi-stage procedure involving a literature review, expert Q-sort and pre-test process, pilot test and survey of 156 supply chain directors and managers in Ireland, we develop a multidimensional conceptualisation and measure of social and environmental supply chain management sustainability practices. The research findings show theoretically sound constructs based on four underlying sustainable supply chain management practices: monitoring, implementing systems, new product and process development and strategy redefinition. A two-factor model is then identified as the most reliable: comprising process-based and market-based practices.

Plastin Polymorphisms Predict Gender- and Stage-Specific Colon Cancer Recurrence after Adjuvant Chemotherapy

Tumor recurrence after curative resection remains a major problem in patients with locally advanced colorectal cancer treated with adjuvant chemotherapy. Genetic single-nucleotide polymorphisms (SNP) may serve as useful molecular markers to predict clinical outcomes in these patients and identify targets for future drug development. Recent in vitro and in vivo studies have demonstrated that the plastin genes PLS3 and LCP1 are overexpressed in colon cancer cells and play an important role in tumor cell invasion, adhesion, and migration. Hence, we hypothesized that functional genetic variations of plastin may have direct effects on the progression and prognosis of locally advanced colorectal cancer. We tested whether functional tagging polymorphisms of PLS3 and LCP1 predict time to tumor recurrence (TTR) in 732 patients (training set, 234; validation set, 498) with stage II/III colorectal cancer. The PLS3 rs11342 and LCP1 rs4941543 polymorphisms were associated with a significantly increased risk for recurrence in the training set. PLS3 rs6643869 showed a consistent association with TTR in the training and validation set, when stratified by gender and tumor location. Female patients with the PLS3 rs6643869 AA genotype had the shortest median TTR compared with those with any G allele in the training set [1.7 vs. 9.4 years; HR, 2.84; 95% confidence interval (CI), 1.32-6.1; P = 0.005] and validation set (3.3 vs. 13.7 years; HR, 2.07; 95% CI, 1.09-3.91; P = 0.021). Our findings suggest that several SNPs of the PLS3 and LCP1 genes could serve as gender- and/or stage-specific molecular predictors of tumor recurrence in stage II/III patients with colorectal cancer as well as potential therapeutic targets.

Expression of proteins associated with hypoxia and Wnt pathway activation is of prognostic significance in hepatocellular carcinoma

In the development and progression of hepatocellular carcinoma, tumor hypoxia plays an important role, as does activation of the Wnt pathway. The aim of this study was to characterize the expression and interrelationship between hypoxia and Wnt-pathway-associated proteins as prognostic factors for hepatocellular carcinoma. Expression of HIF-1α, CA-IX, E-cadherin, β-catenin, and Ki-67 was assessed by immunohistochemistry in 179 primary hepatocellular carcinoma cases. Univariate and multivariate analyses were performed to assess the relationship between the clinicopathological factors, protein expression, overall survival (OS), and recurrence-free survival (RFS). By univariate analysis, tumor stage, size, satellitosis, and vascular invasion were confirmed as prognostic factors for worse OS and RFS. High expression of HIF-1α, CA-IX, β-catenin, Ki-67, and E-cadherin was observed in 60, 15, 64, 8, and 64 % of tumors, respectively, and this was significantly associated with poor OS. CA-IX, HIF-1α, and E-cadherin were independent predictors of poor prognosis. We stratified 169 patients into four groups according to the expression level of hypoxia and Wnt pathway markers. The group with high expression of both hypoxia and Wnt-pathway-associated proteins showed worst OS. The poor survival of this group was also significant in patients with early stage disease and tumor size of less than 5 cm (p < 0.05). We identified a subgroup of hepatocellular carcinoma patients with high expression of both hypoxia and Wnt pathway proteins and found this predictive of poor survival. The therapeutic options for this group might need to be revisited.

All the World's a Stage: Facilitating Discovery Science and Improved Cancer Care through the Global Alliance for Genomics and Health

The recent explosion of genetic and clinical data generated from tumor genome analysis presents an unparalleled opportunity to enhance our understanding of cancer, but this opportunity is compromised by the reluctance of many in the scientific community to share datasets and the lack of interoperability between different data platforms. The Global Alliance for Genomics and Health is addressing these barriers and challenges through a cooperative framework that encourages "team science" and responsible data sharing, complemented by the development of a series of application program interfaces that link different data platforms, thus breaking down traditional silos and liberating the data to enable new discoveries and ultimately benefit patients.

Calmodulin disruption impacts growth and motility in juvenile liver fluke

Background: Deficiencies in effective flukicide options and growing issues with drug resistance make current strategies for liver fluke control unsustainable, thereby promoting the need to identify and validate new control targets in Fasciola spp. parasites. Calmodulins (CaMs) are small calcium-sensing proteins with ubiquitous expression in all eukaryotic organisms and generally use fluctuations in intracellular calcium levels to modulate cell signalling events. CaMs are essential for fundamental processes including the phosphorylation of protein kinases, gene transcription, calcium transport and smooth muscle contraction. In the blood fluke Schistosoma mansoni, calmodulins have been implicated in egg hatching, miracidial transformation and larval development. Previously, CaMs have been identified amongst liver fluke excretory-secretory products and three CaM-like proteins have been characterised biochemically from adult Fasciola hepatica, although their functions remain unknown.

Methods: In this study, we set out to investigate the biological function and control target potential of F. hepatica CaMs (FhCaMs) using RNAi methodology alongside novel in vitro bioassays.

Results: Our results reveal that: (i) FhCaMs are widely expressed in parenchymal cells throughout the forebody region of juvenile fluke; (ii) significant transcriptional knockdown of FhCaM1-3 was inducible by exposure to either long (~200 nt) double stranded (ds) RNAs or 27 nt short interfering (si) RNAs, although siRNAs were less effective than long dsRNAs; (iii) transient long dsRNA exposure-induced RNA interference (RNAi) of FhCaMs triggered transcript knockdown that persisted for ≥ 21 days, and led to detectable suppression of FhCaM proteins; (iv) FhCaM RNAi significantly reduced the growth of juvenile flukes maintained in vitro; (v) FhCaM RNAi juveniles also displayed hyperactivity encompassing significantly increased migration; (vi) both the reduced growth and increased motility phenotypes were recapitulated in juvenile fluke using the CaM inhibitor trifluoperazine hydrochloride, supporting phenotype specificity.

Conclusions: These data indicate that the Ca(2+)-modulating functions of FhCaMs are important for juvenile fluke growth and movement and provide the first functional genomics-based example of a growth-defect resulting from gene silencing in liver fluke. Whilst the phenotypic impacts of FhCaM silencing on fluke behaviour do not strongly support their candidature as new flukicide targets, the growth impacts encourage further consideration, especially in light of the speed of juvenile fluke growth in vivo.

Microbicide Vaginal Rings: Technological Challenges and Clinical Development

Vaginal rings (VRs) are flexible, torus-shaped, polymeric devices designed to sustain delivery of pharmaceutical drugs to the vagina for clinical benefit. Following first report in a 1970 patent application, several steroid-releasing VR products have since been marketed for use in hormone replacement therapy and contraception. Since 2002, there has been growing interest in the use of VR technology for delivery of drugs that can reduce the risk of sexual acquisition of human immunodeficiency virus type 1 (HIV-1), the causative agent of acquired immunodeficiency syndrome (AIDS). Although no vaginally-administered product has yet been approved for HIV reduction/prevention, extensive research efforts are continuing and a number of VR devices offering sustained release of so-called ‘HIV microbicide’ compounds are currently being evaluated in late-stage clinical studies. This review article provides an overview of the published scientific literature within this important field of research, focusing primarily on articles published within peer-reviewed journal publications. Many important aspects of microbicide-releasing VR technology are discussed, with a particular emphasis on the technological, manufacturing and clinical challenges that have emerged in recent years.

The challenge of MNCs and development: oil extraction, CSR, Nigeria and corruption

Globalisation has led to a shift in world order with the rise of the corporate non-state actor. This rise has led to an assumption that Multi-National Corporations (MNCs) must assume responsibilities beyond profit maximisation for shareholders. With the rise of the MNC as a corporate non-state actor there have been discussions around the role of business with regard to human rights.

This article looks at the case of oil extraction in Nigeria. Focussing on the historical dependency of Nigeria and the evolution of the state into a resource-dependent country, it looks at the limitations of existing human rights obligations as they relate to business. This article proposes that corporate social responsibility (CSR) policies of MNCs can act as a preliminary stage in the quest for wider human rights protections. It is in motivating MNCs to design and implement effective CSR policies in dependent states like Nigeria, that the challenge lies.

Microneedle arrays as transdermal and intradermal drug delivery systems: Materials science, manufacture and commercial development

Transdermal drug delivery offers a number of advantages for the patient, due not only its non-invasive and convenient nature, but also factors such as avoidance of first pass metabolism and prevention of gastrointestinal degradation. It has been demonstrated that microneedle arrays can increase the number of compounds amenable to transdermal delivery by penetrating the skin's protective barrier, the stratum corneum, and creating a pathway for drug permeation to the dermal tissue below. Microneedles have been extensively investigated in recent decades for drug and vaccine delivery as well as minimally invasive patient monitoring/diagnosis. This review focuses on a range of critically important aspects of microneedle technology, namely their material composition, manufacturing techniques, methods of evaluation and commercial translation to the clinic for patient benefit and economic return. Microneedle research and development is finally now at the stage where commercialisation is a realistic possibility. However, progress is still required in the areas of scaled-up manufacture and regulatory approval.