Temporal trends in the retention of BVD+ calves and associated animal and herd-level risk factors during the compulsory eradication programme in Ireland

AbstractThe national BVD eradication programme in Ireland started on a voluntary basis in 2012, becoming compulsory in 2013. The programme relies on accurate identification and prompt removal of BVD+ calves. However, a minority of herd owners have chosen to retain BVD+ animals (defined as still being alive more than seven weeks after the date of the initial test), typically with a view to fattening them to obtain some salvage value. During each year of the programme, additional measures have been introduced and implemented to encourage prompt removal of BVD+ animals. The objective of this study was to describe temporal trends in the retention of BVD+ calves and associated animal and herd-level risk factors during the first three years of the compulsory eradication programme in Ireland.The study population included all BVD+ calves born in Ireland in 2013–2015. A parametric survival model was developed to model the time from the initial BVD test until the animal was slaughtered/died on farm or until 31 December 2015 (whichever was earlier). A total of 29,504 BVD+ animals, from 13,917 herds, were included in the study. The proportion of BVD+ animals that were removed from the herd within 7 weeks of the initial test date increased from 43.7% in 2013 to 70.3% in 2015. BVD+ animals born in 2015 had a much lower survival time (median=33days) compared to the 2013 birth cohort (median=62days), with a year on year reduction in survival of BVD+ calves. In the initial parametric survival models, all interactions with herd type were significant. Therefore, separate models were developed for beef and dairy herds. Overall the results of the survival models were similar, with birth year, BVD+ status, herd size, county of birth and birth month consistently identified as risk factors independent of herd type (beef or dairy) or the numbers of BVD+ animals (single or multiple) in the herd. In addition, the presence of a registered mobile telephone number was identified as a risk factor in all models except for dairy herds with a single BVD+, while the sex of the BVD+ calf was only identified as a risk factor in this model.Significant progress has been made in addressing the issue of retention of BVD+ calves, however, there is a need for further improvement. A number of risk factors associated with retention have been identified suggesting areas where future efforts can be addressed

A monoclonal antibody against lymphocyte function-associated antigen-1 decreases HIV-1 replication by inducing the secretion of an antiviral soluble factor

Background: Lymphocyte Function-Associated Antigen-1 (LFA-1) likely plays a role in the pathogenesis of against HIV-1 and is known to facilitate cell-to-cell transmission of the virus. A monoclonal antibody specific for LFA-1 (Cytolin®) was evaluated as a potential therapeutic in pilot studies performed in the mid-1990s. These uncontrolled human studies suggested that administration of this anti-LFA-1 antibody to HIV-1 infected individuals could provide a modest benefit by decreasing circulating HIV-1 RNA and increasing CD4+ T cell counts. At the time, it was proposed that when bound to cytolytic T cells, the antibody inhibited lysis of activated CD4+ T cells. Given the renewed interest in monoclonal antibody therapy for HIV-1 infected individuals, we investigated possible mechanisms of action of this antibody in vitro. Methods: To assess whether this anti-LFA-1 antibody binds to HIV-1, a virus capture assay was performed. Binding of the antibody to cells was assessed using flow cytometry. Inhibition of HIV-1 replication was determined in culture by measuring the amount of p24 produced by ELISA. After co-culture of the antibody with peripheral blood mononuclear cells, supernatants were assayed for cytokines and chemokines using various immunoassays. Results: Our experiments demonstrate that anti-LFA-1 antibody binds to CCR5 and CXCR4 utilizing strains of HIV-1. It also binds to CD8+ T cells and dendritic cells. When bound to virus prior to infection, there is no decrease in HIV-1 replication, suggesting it does not directly inhibit viral replication via virus binding. When bound to cells, it does not inhibit lysis of CD4+ T cells, as was originally hypothesized. Binding to cells does appear to induce the production of a soluble factor that inhibits HIV-1 replication. We determined that this soluble factor was not any of the cytokines or chemokines with known anti-HIV-1 activity. Further, the antibody does not appear to induce any common immune modulating cytokines or chemokines. Conclusions: These results suggest that one possible mechanism of action of this anti-LFA-1 antibody is to inhibit HIV-1 replication via the production of a soluble antiviral factor that is induced upon binding to cells

Evolutionary clade affects resistance of Clostridium difficile spores to Cold Atmospheric Plasma

Clostridium difficile is a spore forming bacterium and the leading cause of colitis and antibiotic associated diarrhoea in the developed world. Spores produced by C. difficile are robust and can remain viable for months, leading to prolonged healthcare-associated outbreaks with high mortality. Exposure of C. difficile spores to a novel, non-thermal atmospheric pressure gas plasma was assessed. Factors affecting sporicidal efficacy, including percentage of oxygen in the helium carrier gas admixture, and the effect on spores from different strains representing the five evolutionary C. difficile clades was investigated. Strains from different clades displayed varying resistance to cold plasma. Strain R20291, representing the globally epidemic ribotype 027 type, was the most resistant. However all tested strains displayed a ~3 log reduction in viable spore counts after plasma treatment for 5 minutes. Inactivation of a ribotype 078 strain, the most prevalent clinical type seen in Northern Ireland, was further assessed with respect to surface decontamination, pH, and hydrogen peroxide concentration. Environmental factors affected plasma activity, with dry spores without the presence of organic matter being most susceptible. This study demonstrates that cold atmospheric plasma can effectively inactivate C. difficile spores, and highlights factors that can affect sporicidal activity

Development of antigen-specific ELISA for circulating autoantibodies to extracellular matrix protein 1 in lichen sclerosus

Lichen sclerosus is a common, acquired chronic inflammatory skin disease of unknown etiology, although circulating autoantibodies to the glycoprotein extracellular matrix protein 1 (ECM1) have been detected in most patients’ sera. We have examined the nature of ECM1 epitopes in lichen sclerosus sera, developed an ELISA system for serologic diagnosis, and assessed clinicopathological correlation between ELISA titer and disease. Epitope-mapping studies revealed that lichen sclerosus sera most frequently recognized the distal second tandem repeat domain and carboxyl-terminus of ECM1. We analyzed serum autoantibody reactivity against this immunodominant epitope in 413 individuals (95 subjects with lichen sclerosus, 161 normal control subjects, and 157 subjects with other autoimmune basement membrane or sclerosing diseases). The ELISA assay was highly sensitive; 76 of 95 lichen sclerosus patients (80.0%) exhibited IgG reactivity. It was also highly specific (93.7%) in discriminating between lichen sclerosus and other disease/control sera. Higher anti-ECM1 titers also correlated with more longstanding and refractory disease and cases complicated by squamous cell carcinoma. Furthermore, passive transfer of affinity-purified patient IgG reproduced some histologic and immunopathologic features of lichen sclerosus skin. This new ELISA is valuable for the accurate detection and quantification of anti-ECM1 autoantibodies. Moreover, the values may have clinical significance in patients with lichen sclerosus

Knocking out ACR2 does not affect arsenic redox status in Arabidopsis thaliana: implications for As detoxification and accumulation in plants

Peer reviewedPublisher PD

Proposed instrumentation for PILOT

PILOT (the Pathfinder for an International Large Optical Telescope) is a proposed Australian/European optical/infrared telescope for Dome C on the Antarctic Plateau, with target first light in 2012. The proposed telescope is 2.4m diameter, with overall focal ratio f/10, and a 1 degree field-of-view. In median seeing conditions, it delivers 0.3" FWHM widefield image quality, from 0.7-2.5 microns. In the best quartile of conditions, it delivers diffraction-limited imaging down to 1 micron, or even less with lucky imaging. The areas where PILOT offers the greatest advantages over existing ground-based telescopes are (a) very high resolution optical imaging, (b) high resolution wide-field optical imaging, and (c) all wide-field thermal infrared imaging. The proposed first generation instrumentation consists of (a) a fast, lownoise camera for diffraction-limited optical lucky imaging; (b) a gigapixel optical camera for seeing-limited imaging over a 1 degree field; (c) a 4K × 4K near-infrared (1-5 micron) camera with both wide-field and diffraction-limited modes; and (d) a double-beamed mid-infrared (7-40 micron) imaging spectrograph

Holding and restraining children for clinical procedures within an acute care setting: an ethical consideration of the evidence

This critical reflection on the ethical concerns of current practice is underpinned by a systematic synthesis of current evidence focusing on why and how children are held or restrained for clinical procedures within acute care and the experiences of those present when a child is held against their wishes. Empirical evidence from a range of clinical settings internationally demonstrates that frequently children are held for procedures to be completed; younger children and those requiring procedures perceived as urgent are more likely to be held. Parents and health professionals express how holding children for procedures can cause feelings of moral distress expressed as uncertainty, guilt and upset and that this act breaches the trusting and protective relationship established with children. Despite this, children’s rights and alternatives to holding are not always respected or explored. Children’s experiences and perceptions are absent from current literature. Children and young people have a moral right to have their voice and protests heard and respected and for these to inform judgements of their best interests and the actions of health professionals. Without robust evidence, debate and recognition that children are frequently held against their wishes in clinical practice for procedures which may not be urgent, children’s rights will continue to be compromised