Neutralizing antibodies against porcine circovirus type 2 in liquid pooled plasma contribute to the biosafety of commercially manufactured spray-dried porcine plasma

Neutralizing antibodies (NA) inherently present in pooled plasma collected at commercial abattoirs may provide some protection against potential porcine circovirus type 2 (PCV2) infectivity of plasma. Moreover, these NA may also contribute to the biosafety of spray-dried porcine plasma (SDPP). The objective of the study was to characterize and quantify the PCV2 antibody neutralizing capacity in pooled liquid porcine plasma and SDPP samples collected from industrial spray-drying facilities located in the Southeast and Midwest regions of the United States and the Northeast region of Spain. In the United States, PCV2 NA was determined in 1 sample of pooled liquid plasma from commercial spray-drying plants in the Southeast and 1 from the Midwest region. Obtained results were compared with those of a plasma sample from a PCV2 vaccinated sow and 1 from a PCV2 antibody negative sow. In Spain, 15 pooled liquid porcine plasma samples and 10 SDPP samples were collected at a commercial spray-drying plant total and NA against PCV2 were determined. Results with pooled liquid porcine plasma from commercial spray-drying facilities in the United States indicated that NA titers against PCV2 in these samples (log2 8.33 ± 0.41 and 9.0 ± 0.0) were similar or greater than the plasma from the PCV2-vaccinated sow (log2 6.33 ± 0.41). The analysis of U.S. samples indicated that liquid plasma diluted to 1:256 (10–2.41) was able to neutralize between 100 to 200 PCV2 virus particles or about 4 logs10 median tissue culture infective dose (TCID50) per milliliter. Similarly, samples from the Spanish pooled liquid plasma and the SDPP samples indicated an increased amount of NA activity against PCV2. Specifically, a dilution of 10–2.47 ± 0.33 of plasma was able to inactivate 100 PCV2 virus particles; therefore, the inactivation capacity of commercial liquid plasma was greater than 104 TCID50/mL. The calculated 90% reduction in infected cells because of NA in pooled plasma samples (log2 8.2 ± 0.38) was less (P < 0.05) than in its concentrate form of SDPP (mean, log2 10.2 ± 0.85). In conclusion, PCV2 NA contained in liquid pooled plasma from market pigs was detected at greater concentrations than that from a vaccinated sow and that after spray-drying biological neutralizing activity was conserved, which implies that the inherent NA in liquid plasma may have an important role in the biosafety of commercially produced SDPP.info:eu-repo/semantics/publishedVersio

Harvest strategy evaluations and co-management for the Moreton Bay Trawl Fishery

Non-Technical Summary Seafood CRC Project 2009/774. Harvest strategy evaluations and co-management for the Moreton Bay Trawl Fishery Principal Investigator: Dr Tony Courtney, Principal Fisheries Biologist Fisheries and Aquaculture, Agri-Science Queensland Department of Agriculture, Fisheries and Forestry Level B1, Ecosciences Precinct, Joe Baker St, Dutton Park, Queensland 4102 Email: [email protected] Project objectives: 1. Review the literature and data (i.e., economic, biological and logbook) relevant to the Moreton Bay trawl fishery. 2. Identify and prioritise management objectives for the Moreton Bay trawl fishery, as identified by the trawl fishers. 3. Undertake an economic analysis of Moreton Bay trawl fishery. 4. Quantify long-term changes to fishing power for the Moreton Bay trawl fishery. 5. Assess priority harvest strategies identified in 2 (above). Present results to, and discuss results with, Moreton Bay Seafood Industry Association (MBSIA), fishers and Fisheries Queensland. Note: Additional, specific objectives for 2 (above) were developed by fishers and the MBSIA after commencement of the project. These are presented in detail in section 5 (below). The project was an initiative of the MBSIA, primarily in response to falling profitability in the Moreton Bay prawn trawl fishery. The analyses were undertaken by a consortium of DAFF, CSIRO and University of Queensland researchers. This report adopted the Australian Standard Fish Names (http://www.fishnames.com.au/). Trends in catch and effort The Moreton Bay otter trawl fishery is a multispecies fishery, with the majority of the catch composed of Greasyback Prawns (Metapenaeus bennettae), Brown Tiger Prawns (Penaeus esculentus), Eastern King Prawns (Melicertus plebejus), squid (Uroteuthis spp., Sepioteuthis spp.), Banana Prawns (Fenneropenaeus merguiensis), Endeavour Prawns (Metapenaeus ensis, Metapenaeus endeavouri) and Moreton Bay bugs (Thenus parindicus). Other commercially important byproduct includes blue swimmer crabs (Portunus armatus), three-spot crabs (Portunus sanguinolentus), cuttlefish (Sepia spp.) and mantis shrimp (Oratosquilla spp.). Logbook catch and effort data show that total annual reported catch of prawns from the Moreton Bay otter trawl fishery has declined to 315 t in 2008 from a maximum of 901 t in 1990. The number of active licensed vessels participating in the fishery has also declined from 207 in 1991 to 57 in 2010. Similarly, fishing effort has fallen from a peak of 13,312 boat-days in 1999 to 3817 boat-days in 2008 – a 71% reduction. The declines in catch and effort are largely attributed to reduced profitability in the fishery due to increased operational costs and depressed prawn prices. The low prawn prices appear to be attributed to Australian aquacultured prawns and imported aquacultured vannamei prawns, displacing the markets for trawl-caught prawns, especially small species such as Greasyback Prawns which traditionally dominated landings in Moreton Bay. In recent years, the relatively high Australian dollar has resulted in reduced exports of Australian wild-caught prawns. This has increased supply on the domestic market which has also suppressed price increases. Since 2002, Brown Tiger Prawns have dominated annual reported landings in the Moreton Bay fishery. While total catch and effort in the bay have declined to historically low levels, the annual catch and catch rates of Brown Tiger Prawns have been at record highs in recent years. This appears to be at least partially attributed to the tiger prawn stock having recovered from excessive effort in previous decades. The total annual value of the Moreton Bay trawl fishery catch, including byproduct, is about $5 million, of which Brown Tiger Prawns account for about$2 million. Eastern King Prawns make up about 10% of the catch and are mainly caught in the bay from October to December as they migrate to offshore waters outside the bay where they contribute to a large mono-specific trawl fishery. Some of the Eastern King Prawns harvested in Moreton Bay may be growth overfished (i.e., caught below the size required to maximise yield or value), although the optimum size-at-capture was not determined in this study. Banana Prawns typically make up about 5% of the catch, but can exceed 20%, particularly following heavy rainfall. Economic analysis of the fishery From the economic survey, cash profits were, on average, positive for both fleet segments in both years of the survey. However, after the opportunity cost of capital and depreciation were taken into account, the residual owner-operator income was relatively low, and substantially lower than the average share of revenue paid to employed skippers. Consequently, owner-operators were earning less than their opportunity cost of their labour, suggesting that the fleets were economically unviable in the longer term. The M2 licensed fleet were, on average, earning similar boat cash profits as the T1/M1 fleet, although after the higher capital costs were accounted for the T1/M1 boats were earning substantially lower returns to owner-operator labour. The mean technical efficiency for the fleet as a whole was estimated to be 0.67. That is, on average, the boats were only catching 67 per cent of what was possible given their level of inputs (hours fished and hull units). Almost one-quarter of observations had efficiency scores above 0.8, suggesting a substantial proportion of the fleet are relatively efficient, but some are also relatively inefficient. Both fleets had similar efficiency distributions, with median technical efficiency score of 0.71 and 0.67 for the M2 and T1/M1 boats respectively. These scores are reasonably consistent with other studies of prawn trawl fleets in Australia, although higher average efficiency scores were found in the NSW prawn trawl fleet. From the inefficiency model, several factors were found to significantly influence vessel efficiency. These included the number of years of experience as skipper, the number of generations that the skipper’s family had been fishing and the number of years schooling. Skippers with more schooling were significantly more efficient than skippers with lower levels of schooling, consistent with other studies. Skippers who had been fishing longer were, in fact, less efficient than newer skippers. However, this was mitigated in the case of skippers whose family had been involved in fishing for several generations, consistent with other studies and suggesting that skill was passed through by families over successive generations. Both the linear and log-linear regression models of total fishing effort against the marginal profit per hour performed reasonably well, explaining between 70 and 84 per cent of the variation in fishing effort. As the models had different dependent variables (one logged and the other not logged) this is not a good basis for model choice. A better comparator is the square root of the mean square error (SMSE) expressed as a percentage of the mean total effort. On this criterion, both models performed very similarly. The linear model suggests that each additional dollar of average profits per hour in the fishery increases total effort by around 26 hours each month. From the log linear model, each percentage increase in profits per hour increases total fishing effort by 0.13 per cent. Both models indicate that economic performance is a key driver of fishing effort in the fishery. The effect of removing the boat-replacement policy is to increase individual vessel profitability, catch and effort, but the overall increase in catch is less than that removed by the boats that must exit the fishery. That is, the smaller fleet (in terms of boat numbers) is more profitable but the overall catch is not expected to be greater than before. This assumes, however, that active boats are removed, and that these were also taking an average level of catch. If inactive boats are removed, then catch of the remaining group as a whole could increase by between 14 and 17 per cent depending on the degree to which costs are reduced with the new boats. This is still substantially lower than historical levels of catch by the fleet. Fishing power analyses An analysis of logbook data from 1988 to 2010, and survey information on fishing gear, was performed to estimate the long-term variation in the fleet’s ability to catch prawns (known as fishing power) and to derive abundance estimates of the three most commercially important prawn species (i.e., Brown Tiger, Eastern King and Greasyback Prawns). Generalised linear models were used to explain the variation in catch as a function of effort (i.e., hours fished per day), vessel and gear characteristics, onboard technologies, population abundance and environmental factors. This analysis estimated that fishing power associated with Brown Tiger and Eastern King Prawns increased over the past 20 years by 10–30% and declined by approximately 10% for greasybacks. The density of tiger prawns was estimated to have almost tripled from around 0.5 kg per hectare in 1988 to 1.5 kg/ha in 2010. The density of Eastern King Prawns was estimated to have fluctuated between 1 and 2 kg per hectare over this time period, without any noticeable overall trend, while Greasyback Prawn densities were estimated to have fluctuated between 2 and 6 kg per hectare, also without any distinctive trend. A model of tiger prawn catches was developed to evaluate the impact of fishing on prawn survival rates in Moreton Bay. The model was fitted to logbook data using the maximum-likelihood method to provide estimates of the natural mortality rate (0.038 and 0.062 per week) and catchability (which can be defined as the proportion of the fished population that is removed by one unit of effort, in this case, estimated to be 2.5 ± 0.4 E-04 per boat-day). This approach provided a method for industry and scientists to develop together a realistic model of the dynamics of the fishery. Several aspects need to be developed further to make this model acceptable to industry. Firstly, there is considerable evidence to suggest that temperature influences prawn catchability. This ecological effect should be incorporated before developing meaningful harvest strategies. Secondly, total effort has to be allocated between each species. Such allocation of effort could be included in the model by estimating several catchability coefficients. Nevertheless, the work presented in this report is a stepping stone towards estimating essential fishery parameters and developing representative mathematical models required to evaluate harvest strategies. Developing a method that allowed an effective discussion between industry, management and scientists took longer than anticipated. As a result, harvest strategy evaluations were preliminary and only included the most valuable species in the fishery, Brown Tiger Prawns. Additional analyses and data collection, including information on catch composition from field sampling, migration rates and recruitment, would improve the modelling. Harvest strategy evaluations As the harvest strategy evaluations are preliminary, the following results should not be adopted for management purposes until more thorough evaluations are performed. The effects, of closing the fishery for one calendar month, on the annual catch and value of Brown Tiger Prawns were investigated. Each of the 12 months (i.e., January to December) was evaluated. The results were compared against historical records to determine the magnitude of gain or loss associated with the closure. Uncertainty regarding the trawl selectivity was addressed using two selectivity curves, one with a weight at 50% selection (S50%) of 7 g, based on research data, and a second with S50% of 14 g, put forward by industry. In both cases, it was concluded that any monthly closure after February would not be beneficial to the industry. The magnitude of the benefit of closing the fishery in either January or February was sensitive to which mesh selectivity curve that was assumed, with greater benefit achieved when the smaller selectivity curve (i.e., S50% = 7 g) was assumed. Using the smaller selectivity (S50% = 7 g), the expected increase in catch value was 10–20% which equates to $200,000 to$400,000 annually, while the larger selectivity curve (S50% = 14 g) suggested catch value would be improved by 5–10%, or $100,000 to$200,000. The harvest strategy evaluations showed that greater benefits, in the order of 30–60% increases in the tiger annual catch value, could have been obtained by closing the fishery early in the year when annual effort levels were high (i.e., > 10,000 boat-days). In recent years, as effort levels have declined (i.e., ~4000 boat-days annually), expected benefits from such closures are more modest. In essence, temporal closures offer greater benefit when fishing mortality rates are high. A spatial analysis of Brown Tiger Prawn catch and effort was also undertaken to obtain a better understanding of the prawn population dynamics. This indicated that, to improve profitability of the fishery, fishers could consider closing the fishery in the period from June to October, which is already a period of low profitability. This would protect the Brown Tiger Prawn spawning stock, increase catch rates of all species in the lucrative pre-Christmas period (November–December), and provide fishers with time to do vessel maintenance, arrange markets for the next season’s harvest, and, if they wish, work at other jobs. The analysis found that the instantaneous rate of total mortality (Z) for the March–June period did not vary significantly over the last two decades. As the Brown Tiger Prawn population in Moreton Bay has clearly increased over this time period, an interesting conclusion is that the instantaneous rate of natural mortality (M) must have increased, suggesting that tiger prawn natural mortality may be density-dependent at this time of year. Mortality rates of tiger prawns for June–October were found to have decreased over the last two decades, which has probably had a positive effect on spawning stocks in the October–November spawning period. Abiotic effects on the prawns The influence of air temperature, rainfall, freshwater flow, the southern oscillation index (SOI) and lunar phase on the catch rates of the four main prawn species were investigated. The analyses were based on over 200,000 daily logbook catch records over 23 years (i.e., 1988–2010). Freshwater flow was more influential than rainfall and SOI, and of the various sources of flow, the Brisbane River has the greatest volume and influence on Moreton Bay prawn catches. A number of time-lags were also considered. Flow in the preceding month prior to catch (i.e., 30 days prior, Logflow1_30) and two months prior (31–60 days prior, Logflow31_60) had strong positive effects on Banana Prawn catch rates. Average air temperature in the preceding 4-6 months (Temp121_180) also had a large positive effect on Banana Prawn catch rates. Flow in the month immediately preceding catch (Logflow1_30) had a strong positive influence on Greasyback Prawn catch rates. Air temperature in the preceding two months prior to catch (Temp1_60) had a large positive effect on Brown Tiger Prawn catch rates. No obvious or marked effects were detected for Eastern King Prawns, although interestingly, catch rates declined with increasing air temperature 4–6 months prior to catch. As most Eastern King Prawn catches in Moreton Bay occur in October to December, the results suggest catch rates decline with increasing winter temperatures. In most cases, the prawn catch rates declined with the waxing lunar phase (high luminance/full moon), and increased with the waning moon (low luminance/new moon). The SOI explains little additional variation in prawn catch rates (~ <2%), although its influence was higher for Banana Prawns. Extrapolating findings of the analyses to long-term climate change effects should be interpreted with caution. That said, the results are consistent with likely increases in abundance in the region for the two tropical species, Banana Prawns and Brown Tiger Prawns, as coastal temperatures rise. Conversely, declines in abundance could be expected for the two temperate species, Greasyback and Eastern King Prawns. Corporate management structures An examination of alternative governance systems was requested by the industry at one of the early meetings, particularly systems that may give them greater autonomy in decision making as well as help improve the marketing of their product. Consequently, a review of alternative management systems was undertaken, with a particular focus on the potential for self-management of small fisheries (small in terms of number of participants) and corporate management. The review looks at systems that have been implemented or proposed for other small fisheries internationally, with a particular focus on self-management as well as the potential benefits and challenges for corporate management. This review also highlighted particular opportunities for the Moreton Bay prawn fishery. Corporate management differs from other co-management and even self-management arrangements in that ‘ownership’ of the fishery is devolved to a company in which fishers and government are shareholders. The company manages the fishery as well as coordinates marketing to ensure that the best prices are received and that the catch taken meets the demands of the market. Coordinated harvesting will also result in increased profits, which are returned to fishers in the form of dividends. Corporate management offers many of the potential benefits of an individual quota system without formally implementing such a system. A corporate management model offers an advantage over a self-management model in that it can coordinate both marketing and management to take advantage of this unique geographical advantage. For such a system to be successful, the fishery needs to be relatively small and self- contained. Small in this sense is in terms of number of operators. The Moreton Bay prawn fishery satisfies these key conditions for a successful self-management and potentially corporate management system. The fishery is small both in terms of number of participants and geography. Unlike other fisheries that have progressed down the self-management route, the key market for the product from the Moreton Bay fishery is right at its doorstep. Corporate management also presents a number of challenges. First, it will require changes in the way fishers operate. In particular, the decision on when to fish and what to catch will be taken away from the individual and decided by the collective. Problems will develop if individuals do not join the corporation but continue to fish and market their own product separately. While this may seem an attractive option to fishers who believe they can do better independently, this is likely to be just a short- term advantage with an overall long-run cost to themselves as well as the rest of the industry. There are also a number of other areas that need further consideration, particularly in relation to the allocation of shares, including who should be allocated shares (e.g. just boat owners or also some employed skippers). Similarly, how harvesting activity is to be allocated by the corporation to the fishers. These are largely issues that cannot be answered without substantial consultation with those likely to be affected, and these groups cannot give these issues serious consideration until the point at which they are likely to become a reality. Given the current structure and complexity of the fishery, it is unlikely that such a management structure will be feasible in the short term. However, the fishery is a prime candidate for such a model, and development of such a management structure in the future should be considered as an option for the longer term

Invariant higher-order variational problems II

Motivated by applications in computational anatomy, we consider a second-order problem in the calculus of variations on object manifolds that are acted upon by Lie groups of smooth invertible transformations. This problem leads to solution curves known as Riemannian cubics on object manifolds that are endowed with normal metrics. The prime examples of such object manifolds are the symmetric spaces. We characterize the class of cubics on object manifolds that can be lifted horizontally to cubics on the group of transformations. Conversely, we show that certain types of non-horizontal geodesics on the group of transformations project to cubics. Finally, we apply second-order Lagrange--Poincar\'e reduction to the problem of Riemannian cubics on the group of transformations. This leads to a reduced form of the equations that reveals the obstruction for the projection of a cubic on a transformation group to again be a cubic on its object manifold.Comment: 40 pages, 1 figure. First version -- comments welcome

Relativistic calculation of nuclear transparency in (e,e'p) reactions

Nuclear transparency in (e,e'p) reactions is evaluated in a fully relativistic distorted wave impulse approximation model. The relativistic mean field theory is used for the bound state and the Pauli reduction for the scattering state, which is calculated from a relativistic optical potential. Results for selected nuclei are displayed in a Q^2 range between 0.3 and 1.8 (GeV/c)^2 and compared with recent electron scattering data. For Q^2 = 0.3 (GeV/c)^2 the results are lower than data; for higher Q^2 they are in reasonable agreement with data. The sensitivity of the model to different prescriptions for the one-body current operator is investigated. The off-shell ambiguities are rather large for the distorted cross sections and small for the plane wave cross sections.Comment: 8 pages, 3 figure

Flux-lattice melting in two-dimensional disordered superconductors

The flux line lattice melting transition in two-dimensional pure and disordered superconductors is studied by a Monte Carlo simulation using the lowest Landau level approximation and quasi-periodic boundary condition on a plane. The position of the melting line was determined from the diffraction pattern of the superconducting order parameter. In the clean case we confirmed the results from earlier studies which show the existence of a quasi-long range ordered vortex lattice at low temperatures. Adding frozen disorder to the system the melting transition line is shifted to slightly lower fields. The correlations of the order parameter for translational long range order of the vortex positions seem to decay slightly faster than a power law (in agreement with the theory of Carpentier and Le Doussal) although a simple power law decay cannot be excluded. The corresponding positional glass correlation function decays as a power law establishing the existence of a quasi-long range ordered positional glass formed by the vortices. The correlation function characterizing a phase coherent vortex glass decays however exponentially ruling out the possible existence of a phase coherent vortex glass phase.Comment: 12 pages, 21 figures, final version to appear in Phys. Rev.

Fast variability from black-hole binaries

Currently available information on fast variability of the X-ray emission from accreting collapsed objects constitutes a complex phenomenology which is difficult to interpret. We review the current observational standpoint for black-hole binaries and survey models that have been proposed to interpret it. Despite the complex structure of the accretion flow, key observational diagnostics have been identified which can provide direct access to the dynamics of matter motions in the close vicinity of black holes and thus to the some of fundamental properties of curved spacetimes, where strong-field general relativistic effects can be observed.Comment: 20 pages, 11 figures. Accepted for publication in Space Science Reviews. Also to appear in hard cover in the Space Sciences Series of ISSI "The Physics of Accretion onto Black Holes" (Springer Publisher

Supermassive Black Hole Binaries: The Search Continues

Gravitationally bound supermassive black hole binaries (SBHBs) are thought to be a natural product of galactic mergers and growth of the large scale structure in the universe. They however remain observationally elusive, thus raising a question about characteristic observational signatures associated with these systems. In this conference proceeding I discuss current theoretical understanding and latest advances and prospects in observational searches for SBHBs.Comment: 17 pages, 4 figures. To appear in the Proceedings of 2014 Sant Cugat Forum on Astrophysics. Astrophysics and Space Science Proceedings, ed. C.Sopuerta (Berlin: Springer-Verlag

2D characterization of near-surface V P/V S: surface-wave dispersion inversion versus refraction tomography

International audienceThe joint study of pressure (P-) and shear (S-) wave velocities (Vp and Vs ), as well as their ratio (Vp /Vs), has been used for many years at large scales but remains marginal in near-surface applications. For these applications, and are generally retrieved with seismic refraction tomography combining P and SH (shear-horizontal) waves, thus requiring two separate acquisitions. Surface-wave prospecting methods are proposed here as an alternative to SH-wave tomography in order to retrieve pseudo-2D Vs sections from typical P-wave shot gathers and assess the applicability of combined P-wave refraction tomography and surface-wave dispersion analysis to estimate Vp/Vs ratio. We carried out a simultaneous P- and surface-wave survey on a well-characterized granite-micaschists contact at Ploemeur hydrological observatory (France), supplemented with an SH-wave acquisition along the same line in order to compare Vs results obtained from SH-wave refraction tomography and surface-wave profiling. Travel-time tomography was performed with P- and SH- wave first arrivals observed along the line to retrieve Vtomo p and Vtomo s models. Windowing and stacking techniques were then used to extract evenly spaced dispersion data from P-wave shot gathers along the line. Successive 1D Monte Carlo inversions of these dispersion data were performed using fixed Vp values extracted from Vtomo p the model and no lateral constraints between two adjacent 1D inversions. The resulting 1D Vsw s models were then assembled to create a pseudo-2D Vsw s section, which appears to be correctly matching the general features observed on the section. If the pseudo-section is characterized by strong velocity incertainties in the deepest layers, it provides a more detailed description of the lateral variations in the shallow layers. Theoretical dispersion curves were also computed along the line with both and models. While the dispersion curves computed from models provide results consistent with the coherent maxima observed on dispersion images, dispersion curves computed from models are generally not fitting the observed propagation modes at low frequency. Surface-wave analysis could therefore improve models both in terms of reliability and ability to describe lateral variations. Finally, we were able to compute / sections from both and models. The two sections present similar features, but the section obtained from shows a higher lateral resolution and is consistent with the features observed on electrical resistivity tomography, thus validating our approach for retrieving Vp/Vs ratio from combined P-wave tomography and surface-wave profiling

Use of Sodium Thiosulfate as an Otoprotectant in Patients With Cancer Treated With Platinum Compounds: A Review of the Literature

PURPOSE Hearing loss occurs in 50%-70% of children treated with cisplatin. Scientific efforts have led to the recent approval of a pediatric formula of intravenous sodium thiosulfate (STS) for otoprotection by the US Food and Drug Administration, the European Medicines Agency, and the Medicines and Health Regulatory Authority in the United Kingdom. To inform stakeholders regarding the clinical utility of STS, the current review summarizes available literature on the efficacy, pharmacokinetics (PK), and safety of systemic STS to minimize cisplatin-induced hearing loss (CIHL). DESIGN A comprehensive narrative review is presented. RESULTS Thirty-one articles were summarized. Overall, systemic STS effectively reduces CIHL in the preclinical and controlled clinical study settings, in both adults and children with cancer. The extent of CIHL reduction depends on the timing and dosing of STS in relation to cisplatin. Both preclinical and clinical data suggest that systemic STS may affect plasma platinum levels, but studies are inconclusive. Delayed systemic administration of STS, at 6 hours after the cisplatin infusion, does not affect cisplatin-induced inhibition of tumor growth or cellular cytotoxicity in the preclinical setting, nor affect cisplatin efficacy and survival in children with localized disease in the clinical setting. CONCLUSION Systemic administration of STS effectively reduces the development and degree of CIHL in both the preclinical and clinical settings. More studies are needed on the PK of STS and cisplatin drug combinations, the efficacy and safety of STS in patients with disseminated disease, and the ability of STS to prevent further deterioration of pre-established hearing loss