Evaluation of absorbent materials for use as ad hoc dry decontaminants during mass casualty incidents as part of the UK's Initial Operational Response (IOR)

The UK's Initial Operational Response (IOR) is a revised process for the medical management of mass casualties potentially contaminated with hazardous materials. A critical element of the IOR is the introduction of immediate, on-scene disrobing and decontamination of casualties to limit the adverse health effects of exposure. Ad hoc cleansing of the skin with dry absorbent materials has previously been identified as a potential means of facilitating emergency decontamination. The purpose of this study was to evaluate the in vitro oil and water absorbency of a range of materials commonly found in the domestic and clinical environments and to determine the effectiveness of a small, but representative selection of such materials in skin decontamination, using an established ex vivo model. Five contaminants were used in the study: methyl salicylate, parathion, diethyl malonate, phorate and potassium cyanide. In vitro measurements of water and oil absorbency did not correlate with ex vivo measurements of skin decontamination. When measured ex vivo, dry decontamination was consistently more effective than a standard wet decontamination method (“rinse-wipe-rinse”) for removing liquid contaminants. However, dry decontamination was ineffective against particulate contamination. Collectively, these data confirm that absorbent materials such as wound dressings and tissue paper provide an effective, generic capability for emergency removal of liquid contaminants from the skin surface, but that wet decontamination should be used for non-liquid contaminants

Managing structural uncertainty in health economic decision models: a discrepancy approach

Healthcare resource allocation decisions are commonly informed by computer model predictions of population mean costs and health effects. It is common to quantify the uncertainty in the prediction due to uncertain model inputs, but methods for quantifying uncertainty due to inadequacies in model structure are less well developed. We introduce an example of a model that aims to predict the costs and health effects of a physical activity promoting intervention. Our goal is to develop a framework in which we can manage our uncertainty about the costs and health effects due to deficiencies in the model structure. We describe the concept of `model discrepancy': the difference between the model evaluated at its true inputs, and the true costs and health effects. We then propose a method for quantifying discrepancy based on decomposing the cost-effectiveness model into a series of sub-functions, and considering potential error at each sub-function. We use a variance based sensitivity analysis to locate important sources of discrepancy within the model in order to guide model refinement. The resulting improved model is judged to contain less structural error, and the distribution on the model output better reflects our true uncertainty about the costs and effects of the intervention

Hybrid in vitro diffusion cell for simultaneous evaluation of hair and skin decontamination: temporal distribution of chemical contaminants

Most casualty or personnel decontamination studies have focused on removing contaminants from the skin. However, scalp hair and underlying skin are the most likely areas of contamination following airborne exposure to chemicals. The aim of this study was to investigate the interactions of contaminants with scalp hair and underlying skin using a hybrid in vitro diffusion cell model. The in vitro hybrid test system comprised “curtains” of human hair mounted onto sections of excised porcine skin within a modified diffusion cell. The results demonstrated that hair substantially reduced underlying scalp skin contamination and that hair may provide a limited decontamination effect by removing contaminants from the skin surface. This hybrid test system may have application in the development of improved chemical incident response processes through the evaluation of various hair and skin decontamination strategies.Peer reviewedFinal Published versio

Initial Effects of Deforestation on Herbaceous Species Composition in Grassy Woodlands of the Northern Tablelands, NSW Australia

Limited information on the initial effects of clearing and thinning on herbaceous vegetation of grassy temperate eucalyptus forests exists. The aim of this investigation is to study the initial changes in species composition following clearing and thinning. A deforestation experiment was established where clearing, thinning of 50% of canopy cover and control treatments were established. In the open-forests, patterns in herbaceous species composition were strongly influenced by the presence of trees, with weeping wheat grass (Microlaena stipoides) dominant, whereas wiregrass (Aristida ramosa) dominated interspaces and canopy gaps. Immediately following clearing, significant changes in the herbaceous species composition were observed, with 26 new species recorded. The original vegetation pattern was lost, being replaced by Cyperaceae and Juncaceae, and a large number of invasive ruderal species. A state and transition model that describes the changes in composition is presented

Genetic therapeutic advancements for Dravet Syndrome

Dravet Syndrome is a genetic epileptic syndrome characterized by severe and intractable seizures associated with cognitive, motor, and behavioral impairments. The disease is also linked with increased mortality mainly due to sudden unexpected death in epilepsy. Over 80% of cases are due to a de novo mutation in one allele of the SCN1A gene, which encodes the α-subunit of the voltage-gated ion channel NaV1.1. Dravet Syndrome is usually refractory to antiepileptic drugs, which only alleviate seizures to a small extent. Viral, non-viral genetic therapy, and gene editing tools are rapidly enhancing and providing new platforms for more effective, alternative medicinal treatments for Dravet syndrome. These strategies include gene supplementation, CRISPR-mediated transcriptional activation, and the use of antisense oligonucleotides. In this review, we summarize our current knowledge of novel genetic therapies that are currently under development for Dravet syndrome

Development of a Grazing Land Management Education Program for Northern Australia’s Grasslands and Grassy Woodlands

Recognition of the potential to enhance grazing land management to meet the goal of sustainable beef production has been increasing over the past decade. Recognition of the relationship between poor land management and negative off-site environmental impacts, such as soil erosion and a decline in the condition of rivers and adjacent near shore coastal areas from sediment transport, has increased also. This concern has matured somewhat to include the critical link between land condition and production, and the threat to sustainable carrying capacity that comes from declining land condition. Concurrently, interest has increased in optimising the use of pasture, e.g. through the development of infrastructure (watering points, fencing), through more pro-active management e.g. alternative grazing systems, spelling of pastures, and through pasture development. In fact, it can be argued that achieving production goals while improving and maintaining the health of the land has become the major on-property issue for northern Australian graziers

The multiple sclerosis risk sharing scheme monitoring study - early results and lessons for the future

Background: Risk sharing schemes represent an innovative and important approach to the problems of rationing and achieving cost-effectiveness in high cost or controversial health interventions. This study aimed to assess the feasibility of risk sharing schemes, looking at long term clinical outcomes, to determine the price at which high cost treatments would be acceptable to the NHS. Methods: This case study of the first NHS risk sharing scheme, a long term prospective cohort study of beta interferon and glatiramer acetate in multiple sclerosis ( MS) patients in 71 specialist MS centres in UK NHS hospitals, recruited adults with relapsing forms of MS, meeting Association of British Neurologists (ABN) criteria for disease modifying therapy. Outcome measures were: success of recruitment and follow up over the first three years, analysis of baseline and initial follow up data and the prospect of estimating the long term cost-effectiveness of these treatments. Results: Centres consented 5560 patients. Of the 4240 patients who had been in the study for a least one year, annual review data were available for 3730 (88.0%). Of the patients who had been in the study for at least two years and three years, subsequent annual review data were available for 2055 (78.5%) and 265 (71.8%) patients respectively. Baseline characteristics and a small but statistically significant progression of disease were similar to those reported in previous pivotal studies. Conclusion: Successful recruitment, follow up and early data analysis suggest that risk sharing schemes should be able to deliver their objectives. However, important issues of analysis, and political and commercial conflicts of interest still need to be addressed

Enhanced expression of the human Survival motor neuron 1 gene from a codon-optimised cDNA transgene in vitro and in vivo

Spinal muscular atrophy (SMA) is a neuromuscular disease particularly characterised by degeneration of ventral motor neurons. Survival motor neuron (SMN) 1 gene mutations cause SMA, and gene addition strategies to replace the faulty SMN1 copy are a therapeutic option. We have developed a novel, codon-optimised hSMN1 transgene and produced integration-proficient and integration-deficient lentiviral vectors with cytomegalovirus (CMV), human synapsin (hSYN) or human phosphoglycerate kinase (hPGK) promoters to determine the optimal expression cassette configuration. Integrating, CMV-driven and codon-optimised hSMN1 lentiviral vectors resulted in the highest production of functional SMN protein in vitro. Integration-deficient lentiviral vectors also led to significant expression of the optimised transgene and are expected to be safer than integrating vectors. Lentiviral delivery in culture led to activation of the DNA damage response, in particular elevating levels of phosphorylated ataxia telangiectasia mutated (pATM) and ?H2AX, but the optimised hSMN1 transgene showed some protective effects. Neonatal delivery of adeno-associated viral vector (AAV9) vector encoding the optimised transgene to the Smn2B/- mouse model of SMA resulted in a significant increase of SMN protein levels in liver and spinal cord. This work shows the potential of a novel codon-optimised hSMN1 transgene as a therapeutic strategy for SMA