Persistent risk for new, subsequent new and recurrent hepatocellular carcinoma despite successful anti-hepatitis B virus therapy and tumor ablation: The need for hepatitis B virus cure.

Hepatitis B virus (HBV) is one of the most significant hepatocarcinogens. The ultimate goal of anti-HBV treatment is to prevent the development of hepatocellular carcinoma (HCC). During the last two decades, with the use of currently available anti-HBV therapies (lamivudine, entecavir and tenofovir disoproxil fumatate), there has been a decrease in the incidence of HBV-associated HCC (HBV-HCC). Furthermore, several studies have demonstrated a reduction in recurrent or new HCC development after initial HCC tumor ablation. However, during an observation period spanning 10 to 20 years, several case reports have demonstrated the development of new, subsequent new and recurrent HCC even in patients with undetectable serum HBV DNA. The persistent risk for HCC is attributed to the presence of covalently closed circular DNA (cccDNA) in the hepatocyte nucleus which continues to work as a template for HBV replication. While a functional cure (loss of hepatitis B surface antigen and undetectable viral DNA) can be attained with nucleos(t)ide analogues, these therapies do not eliminate cccDNA. Of utmost importance is successful eradication of the transcriptionally active HBV cccDNA from hepatocyte nuclei which would be considered a complete cure. The unpredictable nature of HCC development in patients with chronic HBV infection shows the need for a complete cure. Continued support and encouragement for research efforts aimed at developing curative therapies is imperative. The aims of this minireview are to highlight these observations and emphasize the need for a cure for HBV

The Patient Assessment of Chronic Illness Care produces measurements along a single dimension: results from a Mokken analysis.

BACKGROUND: As the worldwide prevalence of chronic illness increases so too does the demand for novel treatments to improve chronic illness care. Quantifying improvement in chronic illness care from the patient perspective relies on the use of validated patient-reported outcome measures. In this analysis we examine the psychometric and scaling properties of the Patient Assessment of Chronic Illness Care (PACIC) questionnaire for use in the United Kingdom by applying scale data to the non-parametric Mokken double monotonicity model. METHODS: Data from 1849 patients with long-term conditions in the UK who completed the 20-item PACIC were analysed using Mokken analysis. A three-stage analysis examined the questionnaire's scalability, monotonicity and item ordering. An automated item selection procedure was used to assess the factor structure of the scale. Analysis was conducted in an 'evaluation' dataset (n = 956) and results were confirmed using an independent 'validation' (n = 890) dataset. RESULTS: Automated item selection procedures suggested that the 20 items represented a single underlying trait representing "patient assessment of chronic illness care": this contrasts with the multiple domains originally proposed. Six items violated invariant item ordering and were removed. The final 13-item scale had no further issues in either the evaluation or validation samples, including excellent scalability (Ho = .50) and reliability (Rho = .88). CONCLUSIONS: Following some modification, the 13-items of the PACIC were successfully fitted to the non-parametric Mokken model. These items have psychometrically robust and produce a single ordinal summary score. This score will be useful for clinicians or researchers to assess the quality of chronic illness care from the patient's perspective

Cardiac output estimation using pulmonary mechanics in mechanically ventilated patients

The application of positive end expiratory pressure (PEEP) in mechanically ventilated (MV) patients with acute respiratory distress syndrome (ARDS) decreases cardiac output (CO). Accurate measurement of CO is highly invasive and is not ideal for all MV critically ill patients. However, the link between the PEEP used in MV, and CO provides an opportunity to assess CO via MV therapy and other existing measurements, creating a CO measure without further invasiveness

Hand performance assessment of ten people with Rheumatoid Arthritis when using a range of specified saucepans

Purpose: The aim of the pilot study was to provide information about the design and use of saucepan handles to enable clinicians and designers to specify and provide products that are more appropriate for use by people with Rheumatoid Arthritis (RA). The objectives were: to evaluate aspects of new handle design for saucepans in terms of their ease of use for people with RA; document hand grip strength and configuration (grip patterns); record relevant anthropometric data to aid the development of new designs and perform an assessment of lifting techniques used in conjunction with perceived optimum handle configuration. Method/Results: Observation and video footage show that subjects continued to use familiar, but damaging, ways of lifting the saucepan even after extensive joint protection training by occupational therapists. Grip strengths recorded using a sphygmomanometer were similar to those found by other studies. The anthropometric measurements taken from the sample group were found to be within available anthropometric surveys of able-bodied people. However, hand length within the sample group with RA was longer than the equivalent in surveys of able-bodied subjects. Conclusions: Subjects preferred the narrower handles with some surface texture to the larger and more rounded tapered handles. Large handled saucepans were found not to be viable due to the constraints of UK cooking hob sizes and existing British Standards relating to saucepan specification

Biowaste and vegetable waste compost application to agriculture

The landfilling of biodegradable waste is proven to contribute to environmental degradation. Compost use in agriculture is increasing as both an alternative to landfilling for the management of biodegradable waste, as well as means of increasing or preserving soil organic matter. This research aimed to contribute to the identification of a system for managing the utilization of vegetable waste (agricultural plant-tissue waste) and biowaste (source-separated biodegradable municipal solid waste) composts for sustainable agriculture, with particular regards to nitrogen availability and leaching.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Integral-based filtering of continuous glucose sensor measurements for glycaemic control in critical care

Hyperglycaemia is prevalent in critical illness and increases the risk of further complications and mortality, while tight control can reduce mortality up to 43%. Adaptive control methods are capable of highly accurate, targeted blood glucose regulation using limited numbers of manual measurements due to patient discomfort and labour intensity. Therefore, the option to obtain greater data density using emerging continuous glucose sensing devices is attractive. However, the few such systems currently available can have errors in excess of 20-30%. In contrast, typical bedside testing kits have errors of approximately 7-10%. Despite greater measurement frequency larger errors significantly impact the resulting glucose and patient specific parameter estimates, and thus the control actions determined creating an important safety and performance issue. This paper models the impact of the Continuous Glucose Monitoring System (CGMS, Medtronic, Northridge, CA) on model-based parameter identification and glucose prediction. An integral-based fitting and filtering method is developed to reduce the effect of these errors. A noise model is developed based on CGMS data reported in the literature, and is slightly conservative with a mean Clarke Error Grid (CEG) correlation of R=0.81 (range: 0.68-0.88) as compared to a reported value of R=0.82 in a critical care study. Using 17 virtual patient profiles developed from retrospective clinical data, this noise model was used to test the methods developed. Monte-Carlo simulation for each patient resulted in an average absolute one-hour glucose prediction error of 6.20% (range: 4.97-8.06%) with an average standard deviation per patient of 5.22% (range: 3.26-8.55%). Note that all the methods and results are generalisable to similar applications outside of critical care, such as less acute wards and eventually ambulatory individuals. Clinically, the results show one possible computational method for managing the larger errors encountered in emerging continuous blood glucose sensors, thus enabling their more effective use in clinical glucose regulation studies

Model for eukaryotic tail-anchored protein binding based on the structure of Get3

The Get3 ATPase directs the delivery of tail-anchored (TA) proteins to the endoplasmic reticulum (ER). TA-proteins are characterized by having a single transmembrane helix (TM) at their extreme C terminus and include many essential proteins, such as SNAREs, apoptosis factors, and protein translocation components. These proteins cannot follow the SRP-dependent co-translational pathway that typifies most integral membrane proteins; instead, post-translationally, these proteins are recognized and bound by Get3 then delivered to the ER in the ATP dependent Get pathway. To elucidate a molecular mechanism for TA protein binding by Get3 we have determined three crystal structures in apo and ADP forms from Saccharomyces cerevisae (ScGet3-apo) and Aspergillus fumigatus (AfGet3-apo and AfGet3-ADP). Using structural information, we generated mutants to confirm important interfaces and essential residues. These results point to a model of how Get3 couples ATP hydrolysis to the binding and release of TA-proteins