The implementation of the Vessel Health and Preservation framework.

Vascular access is an important component of health care but is not without associated risks, some of which can be life-threatening. The Vessel Health and Preservation (VHP) framework was developed with the intention of providing frontline staff with a resource to assist in assessing and selecting the best vascular access device to meet individual patient needs and to preserve veins for future use. This article examines the impact of the introduction of the framework into a haematology ward in an acute hospital in the North West of England during a 3-month pilot study. The results indicate that the VHP framework gave nursing staff more autonomy to choose the appropriate vascular access device for their patients and improved staff knowledge around pH and osmolality of intravenous drugs. However it is clear that more in-depth evaluations need to be conducted to assess the impact of VHP on patient care and outcomes.

Clinical evaluation of a securement device used on midline catheters.

Since the introduction of sutureless securement products for vascular access devices (VADs), there has been a great deal of discussion of their advantages and disadvantages in comparison with sutures. This includes questions related to VAD securement, patients' comfort, infection control, user-friendliness and potential complications of using the device. The literature review of the available evidence indicates the superiority of the novel sutureless devices in the aforementioned aspects. The authors collected data to further contribute in the analysis of the attributes of these products, namely Statlock™ and Grip-Lok™ (current devices). The authors then trialled, collected and analysed data from relevant healthcare practitioners on their perception of a novel sutureless 3M™ Tegaderm™ PICC/CVC Securement Device + Tegaderm™ I.V. Advanced Securement Dressing (trialled device) for midline VADs. Evaluation forms have been provided and filled in by the practitioners. The results showed that the trialled product is perceived as user-and patient-friendly, resulting in increased security of VAD and easier handling compared to the current devices. Overall, 70% of the evaluators stated that the trialled product has better or much better overall performance. The remaining 30% characterised the overall performance comparable with the current devices.

Regulated timber harvesting does not reduce koala density in north-east forests of New South Wales.

The compatibility of forestry and koala conservation is a controversial issue. We used a BACIPS design to assess change in koala density after selective harvesting with regulations to protect environmental values. We also assessed additional sites heavily harvested 5-10 years previously, now dominated by young regeneration. We used replicate arrays of acoustic sensors and spatial count modelling of male bellowing to estimate male koala density over 3600 ha. Paired sites in nearby National Parks served as controls. Naïve occupancy was close to 100% before and after harvesting, indicating koalas were widespread across all arrays. Average density was higher than expected for forests in NSW, varying between arrays from 0.03-0.08 males ha-1. There was no significant effect of selective harvesting on density and little change evident between years. Density 5-10 years after previous heavy harvesting was equivalent to controls, with one harvested array supporting the second highest density in the study. Within arrays, density was similar between areas mapped as selectively harvested or excluded from harvest. Density was also high in young regeneration 5-10 years after heavy harvesting. We conclude that native forestry regulations provided sufficient habitat for koalas to maintain their density, both immediately after selective harvesting and 5-10 years after heavy harvesting.

Rapid generation of an anthrax immunotherapeutic from goats using a novel non-toxic muramyl dipeptide adjuvant.

BACKGROUND: There is a clear need for vaccines and therapeutics for potential biological weapons of mass destruction and emerging diseases. Anthrax, caused by the bacterium Bacillus anthracis, has been used as both a biological warfare agent and bioterrorist weapon previously. Although antibiotic therapy is effective in the early stages of anthrax infection, it does not have any effect once exposed individuals become symptomatic due to B. anthracis exotoxin accumulation. The bipartite exotoxins are the major contributing factors to the morbidity and mortality observed in acute anthrax infections. METHODS: Using recombinant B. anthracis protective antigen (PA83), covalently coupled to a novel non-toxic muramyl dipeptide (NT-MDP) derivative we hyper-immunized goats three times over the course of 14 weeks. Goats were plasmapheresed and the IgG fraction (not affinity purified) and F(ab')2 derivatives were characterized in vitro and in vivo for protection against lethal toxin mediated intoxication. RESULTS: Anti-PA83 IgG conferred 100% protection at 7.5 mug in a cell toxin neutralization assay. Mice exposed to 5 LD50 of Bacillus anthracis Ames spores by intranares inoculation demonstrated 60% survival 14 d post-infection when administered a single bolus dose (32 mg/kg body weight) of anti-PA83 IgG at 24 h post spore challenge. Anti-PA83 F(ab')2 fragments retained similar neutralization and protection levels both in vitro and in vivo. CONCLUSION: The protection afforded by these GMP-grade caprine immunotherapeutics post-exposure in the pilot murine model suggests they could be used effectively to treat post-exposure, symptomatic human anthrax patients following a bioterrorism event. These results also indicate that recombinant PA83 coupled to NT-MDP is a potent inducer of neutralizing antibodies and suggest it would be a promising vaccine candidate for anthrax. The ease of production, ease of covalent attachment, and immunostimulatory activity of the NT-MDP indicate it would be a superior adjuvant to alum or other traditional adjuvants in vaccine formulations.

Broad neutralization and complement-mediated lysis of HIV-1 by PEHRG214, a novel caprine anti-HIV-1 polyclonal antibody.

OBJECTIVES: To assess the potency, breadth of action, and mechanism of action of the polyclonal goat anti-HIV antibody, PEHRG214. DESIGN: Typical human antibody responses to HIV-1 infection are unable to neutralize virus efficiently, clear the infection, or prevent disease progression. However, more potent neutralizing antibodies may be capable of playing a pivotal role in controlling HIV replication in vivo. PEHRG214 is a polyclonal caprine antibody raised against purified HIV-associated proteins, such that epitopes that are immunologically silent in humans may potentially be recognized in another species. It has been administered safely to HIV-infected individuals in Phase I clinical trials. METHODS: The anti-HIV activity of PEHRG214 was assessed using neutralization and virion lysis assays. The target proteins for PEHRG214 activity were investigated using flow cytometry and by adsorption of anti-cell antibodies from the antibody cocktail. RESULTS: PEHRG214 strongly neutralized a diverse range of primary HIV-1 isolates, encompassing subtypes A to E and both CCR5 and CXCR4 phenotypes. Neutralization was enhanced by the presence of complement. PEHRG214 also induced complement-mediated lysis of all HIV-1 isolates tested, and recognized or cross-reacted with a number of host cell proteins. Lysis was abrogated by adsorption with T and/or B cells expressing GPI-linked proteins, but not by GPI-deficient B cells or red blood cells. CONCLUSIONS: PEHRG214 was found to potently neutralize and lyse HIV-1 particles. By targeting host cell proteins present in the viral envelope, which are conserved among all strains tested, PEHRG214 potentially opens up a highly novel means of eliminating circulating virus in infected individuals.

The effects of a subpsychotic dose of ketamine on recognition and source memory for agency: implications for pharmacological modelling of core symptoms of schizophrenia.

Ketamine is increasingly used to model the cognitive deficits and symptoms of schizophrenia. We investigated the extent to which ketamine administration in healthy volunteers reproduces the deficits in episodic recognition memory and agency source monitoring reported in schizophrenia. Intravenous infusions of placebo or 100 ng/ml ketamine were administered to 12 healthy volunteers in a double-blind, placebo-controlled, randomized, within-subjects study. In response to presented words, the subject or experimenter performed a deep or shallow encoding task, providing a 2(drug) x 2(depth of processing) x 2(agency) factorial design. At test, subjects discriminated old/new words, and recalled the sources (task and agent). Data were analyzed using multinomial modelling to identify item recognition, source memory for agency and task, and guessing biases. Under ketamine, item recognition and cued recall of deeply encoded items were impaired, replicating previous findings. In contrast to schizophrenia, there was a reduced tendency to externalize agency source guessing biases under ketamine. While the recognition memory deficit observed with ketamine is consistent with previous work and with schizophrenia, the changes in source memory differ from those reported in schizophrenic patients. This difference may account for the pattern of psychopathology induced by ketamine.

MIS416, a non-toxic microparticle adjuvant derived from Propionibacterium acnes comprising immunostimulatory muramyl dipeptide and bacterial DNA promotes cross-priming and Th1 immunity.

Propionibacterium acnes was modified using biochemical extraction methods generating a suspension of microparticles (MIS416) comprising a minimal cell wall skeleton rich in immunostimulatory crosslinked muramyl dipeptide repeats and native bacterial DNA fragments, each which have known adjuvant activity. In vitro studies demonstrated that MIS416 was readily internalized by human myeloid and plasmacytoid DC inducing cytokine secretion and cell activation/maturation. Vaccination studies in mice using OVA as a model antigen demonstrated that MIS416 acts as a Th1 adjuvant, promoting cross-priming of cytotoxic CD8(+) T cell responses and enhanced anti-tumour immunity. Covalent attachment of OVA to MIS416 enabling simultaneous delivery of antigen and adjuvant to the antigen presentation system resulted in a dose-sparing vaccine formulation. Preclinical GLP toxicology studies demonstrated that MIS416 has a favorable safety profile in mouse and rabbit supporting its use in human vaccine formulations.