Multi-centre evaluation of variation in cumulative dose assessment in reirradiation scenarios.

BACKGROUND AND PURPOSE: Safe reirradiation relies on assessment of cumulative doses to organs at risk (OARs) across multiple treatments. Different clinical pathways can result in inconsistent estimates. Here, we quantified the consistency of cumulative dose to OARs across multi-centre clinical pathways. MATERIAL AND METHODS: We provided DICOM planning CT, structures and doses for two reirradiation cases: head & neck (HN) and lung. Participants followed their standard pathway to assess the cumulative physical and EQD2 doses (with provided α/ß values), and submitted DVH metrics and a description of their pathways. Participants could also submit physical dose distributions from Course 1 mapped onto the CT of Course 2 using their best available tools. To assess isolated impact of image registrations, a single observer accumulated each submitted spatially mapped physical dose for every participating centre. RESULTS: Cumulative dose assessment was performed by 24 participants. Pathways included rigid (n = 15), or deformable (n = 5) image registration-based 3D dose summation, visual inspection of isodose line contours (n = 1), or summation of dose metrics extracted from each course (n = 3). Largest variations were observed in near-maximum cumulative doses (25.4 - 41.8 Gy for HN, 2.4 - 33.8 Gy for lung OARs), with lower variations in volume/dose metrics to large organs. A standardised process involving spatial mapping of the first course dose to the second course CT followed by summation improved consistency for most near-maximum dose metrics in both cases. CONCLUSION: Large variations highlight the uncertainty in reporting cumulative doses in reirradiation scenarios, with implications for outcome analysis and understanding of published doses. Using a standardised workflow potentially including spatially mapped doses improves consistency in determination of accumulated dose in reirradiation scenarios.

Establishment of a yeast-based VLP platform for antigen presentation.

BACKGROUND: Chimeric virus-like particles (VLP) allow the display of foreign antigens on their surface and have proved valuable in the development of safe subunit vaccines or drug delivery. However, finding an inexpensive production system and a VLP scaffold that allows stable incorporation of diverse, large foreign antigens are major challenges in this field. RESULTS: In this study, a versatile and cost-effective platform for chimeric VLP development was established. The membrane integral small surface protein (dS) of the duck hepatitis B virus was chosen as VLP scaffold and the industrially applied and safe yeast Hansenula polymorpha (syn. Pichia angusta, Ogataea polymorpha) as the heterologous expression host. Eight different, large molecular weight antigens of up to 412 amino acids derived from four animal-infecting viruses were genetically fused to the dS and recombinant production strains were isolated. In all cases, the fusion protein was well expressed and upon co-production with dS, chimeric VLP containing both proteins could be generated. Purification was accomplished by a downstream process adapted from the production of a recombinant hepatitis B VLP vaccine. Chimeric VLP were up to 95% pure on protein level and contained up to 33% fusion protein. Immunological data supported surface exposure of the foreign antigens on the native VLP. Approximately 40 mg of chimeric VLP per 100 g dry cell weight could be isolated. This is highly comparable to values reported for the optimized production of human hepatitis B VLP. Purified chimeric VLP were shown to be essentially stable for 6 months at 4 °C. CONCLUSIONS: The dS-based VLP scaffold tolerates the incorporation of a variety of large molecular weight foreign protein sequences. It is applicable for the display of highly immunogenic antigens originating from a variety of pathogens. The yeast-based production system allows cost-effective production that is not limited to small-scale fundamental research. Thus, the dS-based VLP platform is highly efficient for antigen presentation and should be considered in the development of future vaccines.

Cost-Effectiveness Analysis of a Military Hearing Conservation Program.

INTRODUCTION: Occupational noise threatens U.S. worker health and safety and commands a significant financial burden on state and federal government worker compensation programs. Previous studies suggest that hearing conservation programs have contributed to reduced occupational hearing loss for noise-exposed workers. Many military personnel are overexposed to noise and are provided hearing conservation services. Select military branches require all active duty personnel to follow hearing conservation program guidelines, regardless of individual noise exposure. We evaluated the cost-effectiveness of a military hearing conservation program, relative to no intervention, in relation to cases of hearing loss prevented. METHODS: We employed cost-effectiveness analytic methods to compare the costs and effectiveness, in terms of hearing loss cases prevented, of a military hearing conservation program relative to no program. We used costs and probability estimates available in the literature and publicly available sources. The effectiveness of the interventions was analyzed based on whether hearing loss occurred over a 20-yr time frame. RESULTS: The incremental cost-effectiveness ratio of the hearing conservation program compared with no intervention was $10,657 per case of hearing loss prevented. Workers were 28% less likely to sustain hearing loss in our model when they received the hearing conservation program compared with no intervention, which reflected the greater effectiveness of the hearing conservation program. Cost-effectiveness results were sensitive to estimated values for the probability of acquiring hearing loss from both interventions and the cost of hearing protection. We performed a Monte Carlo probabilistic sensitivity analysis where we simultaneously varied all the model parameters to their extreme plausible bounds. When we ran 10,000 Monte Carlo iterations, we observed that the hearing conservation program was more cost-effective in 99% of cases when decision makers were willing to pay $64,172 per case of hearing loss prevented. CONCLUSIONS: Conceding a lifetime cost for service-related compensation for hearing loss per individual of $64,172, the Department of Defense Hearing Conservation Program is an economically reasonable program relative to no intervention, if a case of hearing loss avoided costs $10,657. Considering the net difference of the costs and comparative benefits of both treatment strategies, providing a hearing conservation program for all active duty military workers may be a cost-effective intervention for the Department of Defense.

Quality assessment of commercially processed carbon monoxide-treated tilapia fillets.

Carbon monoxide (CO) has been used to stabilize the color of fish muscle during frozen storage and distribution. This study compared changes in the quality profiles of CO-treated and untreated (UT) tilapia fillets stored at 21 to 22 °C (room temperature), 4 to 5 °C (refrigerated), and 0 °C (iced). Samples (n = 3) were analyzed at different time intervals for chemical, lipid oxidation, microbiological, color, and expert sensory profiles. CO samples contained greater (P < 0.05) apparent ammonia and total volatile base nitrogen (TVB-N) at day 0, with greater (P < 0.05) TVB-N throughout refrigerated and iced storage. At time 0, peroxide values (POV) and thiobarbituric-acid-reactive substances were lower (P < 0.05) for CO samples and continued to have lower trends throughout all storage temperatures. Microbiological analysis at time 0 did not show any differences between UT and CO samples. Redness (a*) color values were greater (P < 0.05) in CO tilapia at time 0; however, treated product showed a more rapid decline in a* throughout all storage temperatures. While expert sensory evaluation showed no statistical differences between UT and CO tilapia at time 0, CO product failed sensory assessment sooner than UT product when stored refrigerated and in ice.

Quality assessment of filtered smoked yellowfin tuna (Thunnus albacares) steaks.

UNLABELLED: Filtered smoke (FS) has been used to preserve taste, texture, and/or color in tuna and other fish species. This treatment is particularly important in color preservation during frozen storage. The objective of this study was to compare changes in the quality profiles of FS-treated and untreated (UT) yellowfin tuna (Thunnus albacares) steaks stored in 3 ways: room temperature (21 to 22 °C), refrigerated (4 to 5 °C), and iced (0 °C). FS and UT steaks were processed from the same lot of fish and analyzed for chemical, microbiological, lipid oxidation, color, and sensory profiles. Similar trends were seen for microbial proliferation and accumulation of apparent ammonia and total volatile base nitrogen (TVB-N) during the storage temperatures evaluated. Notable exception in quality profile was found in lipid oxidation which was, as expected, lower for treated samples at all storage temperatures for TBARS (P < 0.05) and lower or significantly (P < 0.05) lower for POV values. FS increased the initial redness value significantly (P < 0.05). Unlike UT product, there was no loss of color value concomitant with quality changes for FS-treated tuna for all storage temperatures evaluated. PRACTICAL APPLICATION: The overall goal of this project was to evaluate filtered smoked tuna steaks as to the impact on the overall quality profile. As a color-stabilizing technology, it could mask deteriorating quality.