Hepatitis B virus-specific CD4 T cell responses differentiate functional cure from chronic surface antigen+ infection.

BACKGROUND & AIMS: With or without antiviral treatment, few individuals achieve sustained functional cure of chronic hepatitis B virus (HBV) infection. A better definition of what mediates functional cure is essential for improving immunotherapeutic strategies. We aimed to compare HBV-specific T cell responses in patients with different degrees of viral control. METHODS: We obtained blood from 124 HBV-infected individuals, including those with acute self-limiting HBV infection, chronic infection, and chronic infection with functional cure. We screened for HBV-specific T cell specificities by ELISpot, assessed the function of HBV-specific T cells using intracellular cytokine staining, and characterized HBV-specific CD4 T cells using human leukocyte antigen (HLA) class II tetramer staining, all directly ex vivo. RESULTS: ELISpot screening readily identified HBV-specific CD4 and CD8 T cell responses in acute resolving infection compared with more limited reactivity in chronic infection. Applying more sensitive assays revealed higher frequencies of functional HBV-specific CD4 T cells, but not CD8 T cells, in functional cure compared to chronic infection. Function independent analysis using HLA multimers also identified more HBV-specific CD4 T cell responses in functional cure compared to chronic infection, with the emergence of CD4 T cell memory both after acute and chronic infection. CONCLUSIONS: Functional cure is associated with higher frequencies of functional HBV-specific CD4 memory T cell responses. Thus, immunotherapeutic approaches designed to induce HBV functional cure should also aim to improve CD4 T cell responses. LAY SUMMARY: Immunotherapy is a form of treatment that relies on harnessing the power of an individual's immune system to target a specific disease or pathogen. Such approaches are being developed for patients with chronic HBV infection, in an attempt to mimic the immune response in patients who control HBV infection spontaneously, achieving a so-called functional cure. However, what exactly defines protective immune responses remains unclear. Herein, we show that functional cure is associated with robust responses by HBV-specific CD4 T cells (a type of immune cell).

Delivering Behaviour Change Interventions: Development of a Mode of Delivery Ontology.

Background: Investigating and improving the effects of behaviour change interventions requires detailed and consistent specification of all aspects of interventions. An important feature of interventions is the way in which these are delivered, i.e. their mode of delivery. This paper describes an ontology for specifying the mode of delivery of interventions, which forms part of the Behaviour Change Intervention Ontology, currently being developed in the Wellcome Trust funded Human Behaviour-Change Project. Methods: The Mode of Delivery Ontology was developed in an iterative process of annotating behaviour change interventions evaluation reports, and consulting with expert stakeholders. It consisted of seven steps: 1) annotation of 110 intervention reports to develop a preliminary classification of modes of delivery; 2) open review from international experts (n=25); 3) second round of annotations with 55 reports to test inter-rater reliability and identify limitations; 4) second round of expert review feedback (n=16); 5) final round of testing of the refined ontology by two annotators familiar and two annotators unfamiliar with the ontology; 6) specification of ontological relationships between entities; and 7) transformation into a machine-readable format using the Web Ontology Language (OWL) language and publishing online. Results: The resulting ontology is a four-level hierarchical structure comprising 65 unique modes of delivery, organised by 15 upper-level classes: Informational , Environmental change, Somatic, Somatic alteration, Individual-based/ Pair-based /Group-based, Uni-directional/Interactional, Synchronous/ Asynchronous, Push/ Pull, Gamification, Arts feature. Relationships between entities consist of is_a. Inter-rater reliability of the Mode of Delivery Ontology for annotating intervention evaluation reports was a=0.80 (very good) for those familiar with the ontology and a= 0.58 (acceptable) for those unfamiliar with it. Conclusion: The ontology can be used for both annotating and writing behaviour change intervention evaluation reports in a consistent and coherent manner, thereby improving evidence comparison, synthesis, replication, and implementation of effective interventions.

Comparison of radium-228 determination in water among Australian laboratories.

The National Health and Medical Research Council and Natural Resource Management Ministerial Council of Australia developed the current Australian Drinking Water Guidelines which recommend an annual radiation dose value of 1 mSv year-1. One of the potential major contributors to the radiation dose from drinking water is radium-228, a naturally occurring radionuclide arising from the thorium decay series. Various methods of analysing for radium-228 in water have been established and adapted by analytical radiochemistry laboratories. Seven laboratories in Australia participated in analysing radium-228 spiked water samples with activity concentrations ranging from 6 mBq L-1 to 20 Bq L-1. The aim of the exercise was to compare and evaluate radium-228 results reported by the participating laboratories, the methods used and the detection limits. This paper presents the outcome of the exercise.

Natural radionuclides and stable elements in weaver ants (Oecophylla smaragdina) from tropical northern Australia.

Natural radionuclides and stable elements were measured in weaver ants, leaves and soils collected from three sites in tropical northern Australia. Radionuclide concentration ratios for ants relative to soil were derived from the measurements and used to refine the current environmental radiological assessment for remediation of Ranger uranium mine. Use of site-specific concentration ratios for weaver ants gave a more conservative estimate of environmental exposure to the arthropod wildlife group than use of default concentration ratios in the ERICA Tool. This was primarily because the 226Ra concentration ratio for weaver ants was more than 7 times greater than for generic arthropods.

High-throughput diagnosis of potato cyst nematodes in soil samples.

Potato cyst nematode (PCN) is a damaging soilborne pest of potatoes which can cause major crop losses. In 2010, a new European Union directive (2007/33/EC) on the control of PCN came into force. Under the new directive, seed potatoes can only be planted on land which has been found to be free from PCN infestation following an official soil test. A major consequence of the new directive was the introduction of a new harmonized soil sampling rate resulting in a threefold increase in the number of samples requiring testing. To manage this increase with the same staffing resources, we have replaced the traditional diagnostic methods. A system has been developed for the processing of soil samples, extraction of DNA from float material, and detection of PCN by high-throughput real-time PCR. Approximately 17,000 samples are analyzed each year using this method. This chapter describes the high-throughput processes for the production of float material from soil samples, DNA extraction from the entire float, and subsequent detection and identification of PCN within these samples.

Molecular and serological methods for the diagnosis of viruses in potato tubers.

Viruses cause important diseases to potato crops. Monitoring virus content in plant material for quarantine or seed certification scheme purposes is essential to prevent the spread of viruses and to minimize the impact of viral diseases. There are currently two main methods for virus diagnosis in potato tubers: growing-on ELISA testing which requires breaking tuber dormancy followed by an ELISA test on grown plantlets and direct real-time RT-PCR testing on tubers. This chapter will describe both methods that can be adapted for large-scale virus testing activities.

Assessing eradication strategies for rain-splashed and wind-dispersed crop diseases.

BACKGROUND: The eradicability of rain-splashed crop diseases was examined by modelling the spread of lupin anthracnose over a spatially heterogeneous landscape. Two hypotheses were investigated: (i) in most cases, rain-splashed diseases are unlikely to be eradicable because spread will be too extensive by the time the disease is detected; (ii) there are recognisable characteristics of an incursion that can be used to identify cases when the disease will be eradicable. RESULTS: Results indicate that the eradication of a rain-splashed crop disease is heavily dependent on the surveillance effort, on how detectable the disease is and on whether there are susceptible hosts outside the cropping area. These simple indicators can be used to estimate the potential for success of an eradication scheme. Eradication targeting only the crop area is destined to fail, unless it is certain that no susceptible host lies adjacent to the cropping area. CONCLUSION: A failed eradication attempt can be costly, and a simple set of indicators for the likelihood of success is extremely useful. These indicators can aid decision-makers when faced with a new incursion, identifying when there is little hope of success. © 2012 Society of Chemical Industry.