Blending: consequences for wheat breeding

Established and supported under the Australian Government’s Cooperative Research Centre Progra

Rapid Electrophoretic Verification of Varietal Identity: Application to 30 Current Australian Wheats

Established and supported under the Australian Government’s Cooperative Research Centre Progra

Arnotts Blending Project

Established and supported under the Australian Government’s Cooperative Research Centre Progra

Infected dendritic cells are sufficient to mediate the adjuvant activity generated by Venezuelan equine encephalitis virus replicon particles

Replicon particles derived from Venezuelan equine encephalitis virus (VEE) are infectious non-propagating particles which act as a safe and potent systemic, mucosal, and cellular adjuvant when delivered with antigen. VEE and VEE replicon particles (VRP) can target multiple cell types including dendritic cells (DCs). The role of these cell types in VRP adjuvant activity has not been previously evaluated, and for these studies we focused on the contribution of DCs to the response to VRP. By analysis of VRP targeting in the draining lymph node, we found that VRP induced rapid recruitment of TNF-secreting monocyte-derived inflammatory dendritic cells. VRP preferentially infected these inflammatory DCs as well as classical DCs and macrophages, with less efficient infection of other cell types. DC depletion suggested that the interaction of VRP with classical DCs was required for recruitment of inflammatory DCs, induction of high levels of many cytokines, and for stable transport of VRP to the draining lymph node. Additionally, in vitro-infected DCs enhanced antigen-specific responses by CD4 and CD8 T cells. By transfer of VRP-infected DCs into mice we showed that these DCs generated an inflammatory state in the draining lymph node similar to that achieved by VRP injection. Most importantly, VRP-infected DCs were sufficient to establish robust adjuvant activity in mice comparable to that produced by VRP injection. These findings indicate that VRP infect, recruit and activate both classical and inflammatory DCs, and those DCs become mediators of the VRP adjuvant activity

Point-of-care tests for infectious diseases: barriers to implementation across three London teaching hospitals.

Existing Point-of-care tests (POCT) to help identify infection-related causes of illness can complement diagnostic and disposition decisions in children attending emergency departments.(1) Evidence-based clinical algorithms can integrate such POCT to aid in the admission and discharge decision process. Paediatric studies validating these tools are scarce, with very few studies conducted in UK centres.(2-5) POCT can be based on host infection markers (e.g. finger prick tests for C-reactive protein (CRP) to help decide if the patient has a bacterial or viral infection) or pathogen detection tests (e.g. throat/nose swabs to rapidly diagnose viral infections such as RSV or influenza). This article is protected by copyright. All rights reserved

Dietary protein intake, breast feeding and growth in human milk fed preterm infants

Protein intakes of preterm infants are frequently below recommendations, but few studies report accurate intakes due to the difficulty of analysing human milk clinically. This observational analysis from a randomised trial of infants born <31 weeks’ gestation, investigating two levels of protein fortification, reports protein intakes compared with requirements and determines the association of direct breastfeeding on growth. Ninety-two infants (median gestational age 28 weeks, Interquartile range (IQR) 26–29; mean birth weight 1040 g, SD 300 g) were studied. Infants born weighing <1000 g were underfed protein compared with recommendations (median (IQR) intake of 3.0 (2.0–3.7) g/kg/day in week 2 versus recommendation of 4–4.5 g/kg/day), while those born weighing ≥1000 g met recommended protein intakes after the first week of life (median (IQR) intake of 3.7 (3.0–4.0) g/kg/day in week 2 versus recommendation of 3.5–4.5 g/kg/day). A moderate, negative correlation between the mean number of breast feeds and change in rate of weight gain (r = −0.37, p = 0.001) was found. Protein intakes of infants <1000 g did not meet recommendations and all infants were underfed protein and energy in the first week of life. Current protein fortification is inadequate for infants born <1000 g. Exploratory analysis showed faltering rate weight gain associated with increasing number of breast feeds and these results warrant confirmation.Emma Tonkin, Jacqueline Miller, Maria Makrides, Andrew J. McPhee, Scott A. Morris, Robert A. Gibson and Carmel T. Collin

An Alphavirus-Based Adjuvant Enhances Serum and Mucosal Antibodies, T Cells, and Protective Immunity to Influenza Virus in Neonatal Mice

Neonatal immune responses to infection and vaccination are biased toward TH2 at the cost of proinflammatory TH1 responses needed to combat intracellular pathogens. However, upon appropriate stimulation, the neonatal immune system can induce adult-like TH1 responses. Here we report that a new class of vaccine adjuvant is especially well suited to enhance early life immunity. The GVI3000 adjuvant is a safe, nonpropagating, truncated derivative of Venezuelan equine encephalitis virus that targets dendritic cells (DCs) in the draining lymph node (DLN) and produces intracellular viral RNA without propagating to other cells. RNA synthesis strongly activates the innate immune response so that in adult animals, codelivery of soluble protein antigens induces robust humoral, cellular, and mucosal responses. The adjuvant properties of GVI3000 were tested in a neonatal BALB/c mouse model using inactivated influenza virus (iFlu). After a single immunization, mice immunized with iFlu with the GVI3000 adjuvant (GVI3000-adjuvanted iFlu) had significantly higher and sustained influenza virus-specific IgG antibodies, mainly IgG2a (TH1), compared to the mice immunized with antigen only. GVI3000 significantly increased antigen-specific CD4+ and CD8+ T cells, primed mucosal immune responses, and enhanced protection from lethal challenge. As seen in adult mice, the GVI3000 adjuvant increased the DC population in the DLNs, caused activation and maturation of DCs, and induced proinflammatory cytokines and chemokines in the DLNs soon after immunization, including gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), granulocyte colony-stimulating factor (G-CSF), and interleukin 6 (IL-6). In summary, the GVI3000 adjuvant induced an adult-like adjuvant effect with an influenza vaccine and has the potential to improve the immunogenicity and protective efficacy of new and existing neonatal vaccines

Alphavirus replicon-based enhancement of mucosal and systemic immunity is linked to the innate response generated by primary immunization

Venezuelan equine encephalitis virus replicon particles (VRP) function as an effective systemic, cellular and mucosal adjuvant when codelivered with antigen, and show promise for use as a component in new and existing human vaccine formulations. We show here that VRP are effective at low dose and by intramuscular delivery, two useful features for implementation of VRP as a vaccine adjuvant. In mice receiving a prime and boost with antigen, we found that VRP are required in prime only to produce a full adjuvant effect. This outcome indicates that the events triggered during prime with VRP are sufficient to establish the nature and magnitude of the immune response to a second exposure to antigen. Events induced by VRP in the draining lymph node after prime include robust secretion of many inflammatory cytokines, upregulation of CD69 on leukocytes, and increased cellularity, with a disproportionate increase of a cell population expressing CD11c, CD11b, and F4/80. We show that antigen delivered 24 hours after administration of VRP does not benefit from an adjuvant effect, indicating that the events which are critical to VRP-mediated adjuvant activity occur within the first 24 hours. Further studies of the events induced by VRP will help elucidate the mechanism of VRP adjuvant activity and will advance the safe implementation of this adjuvant in human vaccines

Patterns and predictors of adherence to statin therapy among older patients: Protocol for a systematic review

Background: The benefits of statin therapy are significantly compromised by noncompliance. Although elderly patients may have particular challenges with medication adherence and persistence, previous reviews on statin adherence have not focused on this population. Additionally, comparisons of adherence and persistence specific to statin indication (primary or secondary prevention) have not been thoroughly explored.Objective: We aim to assess the extent of, and factors associated with, adherence and persistence to statin therapy among older populations (aged ≥65 years).Methods: A systematic review will be undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. Searches will be performed using multiple electronic databases (Ovid MEDLINE, EMBASE, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, and the National Health Service Economic Evaluation Database) to identify relevant randomized trials and observational studies that evaluated statin adherence and/or persistence as an outcome. Eligible studies will include those involving community-living or outpatient elderly individuals. The methodological quality of randomized controlled trials (RCTs) will be assessed via the Joanna Briggs Institute's critical appraisal checklist for RCTs, and the quality assessment of observational studies will be undertaken using a set of questions formulated with resort to the National Institute of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. When possible, meta-analyses will be conducted using random-effect modeling and generic inverse variance analyses for adjusted-effect estimates. Heterogeneity across studies will be quantified using the I2 statistic. The presence of publication bias will be assessed using funnel plots and Egger's regression tests. A leave-one-out sensitivity analysis will also be conducted to assess the impact of individual study results on pooled estimates. To explore possible sources of heterogeneity across studies, subgroup analyses will be performed based on covariates such as study design, statin indication, country of study, and length of patient follow-up.Results: The electronic database searches were completed in December 2016. Retrieved articles are currently being screened and the entire study is expected to be completed by June 2017.Conclusions: This systematic review will provide further understanding of the patterns of, and barriers to, statin adherence and persistence among older patients. The findings will inform clinical practice and the design of appropriate interventions