Some considerations on the dependence to numerical schemes of Lagrangian radionuclide transport models for the aquatic environment.

Lagrangian models present several advantages over Eulerian models to simulate the transport of radionuclides in the aquatic environment in emergency situations. A radionuclide release is simulated as a number of particles whose trajectories are calculated along time and thus these models do not require a spatial discretization (although it is always required in time). In this paper we investigate the dependence of a Lagrangian model output with the grid spacing which is used to calculate concentrations from the final distribution of particles, with the number of particles in the simulation and with the interpolation schemes which are required because of the discrete nature of the water circulation data used to feed the model. Also, a Lagrangian model may describe the exchanges of radionuclides between phases (liquid and solid), which is done in terms of transition probabilities. The dependence of these probabilities with time step is analyzed as well. It was found that the optimum grid size used to calculate concentrations should be carefully checked, and that temporal interpolation is more significant than spatial interpolation to obtain a more accurate solution. A method to estimate the number of particles required to have a certain accuracy level is proposed. Finally, it was found that for low sediment concentrations and small radionuclide kd, exact equations for the transition probabilities should be used; and that phase transitions introduce a stability condition as in Eulerian models.

Third international challenge to model the medium- to long-range transport of radioxenon to four Comprehensive Nuclear-Test-Ban Treaty monitoring stations.

In 2015 and 2016, atmospheric transport modeling challenges were conducted in the context of the Comprehensive Nuclear-Test-Ban Treaty (CTBT) verification, however, with a more limited scope with respect to emission inventories, simulation period and number of relevant samples (i.e., those above the Minimum Detectable Concentration (MDC)) involved. Therefore, a more comprehensive atmospheric transport modeling challenge was organized in 2019. Stack release data of Xe-133 were provided by the Institut National des Radioéléments/IRE (Belgium) and the Canadian Nuclear Laboratories/CNL (Canada) and accounted for in the simulations over a three (mandatory) or six (optional) months period. Best estimate emissions of additional facilities (radiopharmaceutical production and nuclear research facilities, commercial reactors or relevant research reactors) of the Northern Hemisphere were included as well. Model results were compared with observed atmospheric activity concentrations at four International Monitoring System (IMS) stations located in Europe and North America with overall considerable influence of IRE and/or CNL emissions for evaluation of the participants' runs. Participants were prompted to work with controlled and harmonized model set-ups to make runs more comparable, but also to increase diversity. It was found that using the stack emissions of IRE and CNL with daily resolution does not lead to better results than disaggregating annual emissions of these two facilities taken from the literature if an overall score for all stations covering all valid observed samples is considered. A moderate benefit of roughly 10% is visible in statistical scores for samples influenced by IRE and/or CNL to at least 50% and there can be considerable benefit for individual samples. Effects of transport errors, not properly characterized remaining emitters and long IMS sampling times (12-24 h) undoubtedly are in contrast to and reduce the benefit of high-quality IRE and CNL stack data. Complementary best estimates for remaining emitters push the scores up by 18% compared to just considering IRE and CNL emissions alone. Despite the efforts undertaken the full multi-model ensemble built is highly redundant. An ensemble based on a few arbitrary runs is sufficient to model the Xe-133 background at the stations investigated. The effective ensemble size is below five. An optimized ensemble at each station has on average slightly higher skill compared to the full ensemble. However, the improvement (maximum of 20% and minimum of 3% in RMSE) in skill is likely being too small for being exploited for an independent period.

The transport, effective half-lives and age distributions of radioactive releases in the northern Indian Ocean.

A Lagrangian model which describes radionuclide transport in the northern Indian Ocean is described. Water circulation is obtained from HYCOM ocean model for year 2017. The model includes advection by currents, turbulent mixing and radionuclide interactions between water and sediments, described in a dynamic way using kinetic transfer coefficients. Hypothetical releases from five coastal nuclear power plants operating in the northern Indian Ocean were simulated. Releases were supposed to start both during the winter and summer monsoons, to study reversing circulation effects. Age distributions of releases were calculated, which adds information about circulation and radionuclide pathways. It was found that, for some of the NPPs, radionuclide distributions resulting from releases starting in both seasons were not as different as could be expected from the opposed circulation schemes during each monsoon. Effective 137Cs half-lives in the ocean surface were calculated and results were two orders of magnitude below previous estimations.

De Novo Hepatitis B Virus Infection After Liver Transplantation in Hepatitis B Core-positive Recipients Using Hepatitis B Core-negative Grafts.

BACKGROUND: Hepatitis B core antibody-positive (HBcAb+) graft is known as a risk for de novo hepatitis B virus (HBV) infection in recipients after liver transplantation (LT). However, little is known about the possibility or incidence of de novo HBV infections after LT in hepatitis B surface antigen-negative (HBsAg-)/HBcAb+ recipients using HBsAg-/HBcAb- grafts. The study aimed to evaluate the prevalence of de novo HBV infection in HBsAg-/HBcAb+ recipients using HBsAg-/HBcAb- grafts. A retrospective review was performed with the records of 1129 adult patients who underwent primary LT at a single institution in an HBV endemic area between January 2000 and December 2013. A total of 78 patients (6.9%) were reviewed for de novo HBV infection after LT. De novo HBV infection was developed in 1 patient (1.28%). The patient was a 65-year-old woman who underwent LT due to alcoholic liver cirrhosis. De novo HBV was not related to graft loss or death and well treated with tenofovir. In conclusion, de novo HBV infections may occur in HBsAg-/HBcAb+ recipients using HBsAg-/HBcAb- grafts, and caution is needed in these patients.

Fukushima 137Cs releases dispersion modelling over the Pacific Ocean. Comparisons of models with water, sediment and biota data.

A number of marine radionuclide dispersion models (both Eulerian and Lagrangian) were applied to simulate 137Cs releases from Fukushima Daiichi nuclear power plant accident in 2011 over the Pacific at oceanic scale. Simulations extended over two years and both direct releases into the ocean and deposition of atmospheric releases on the ocean surface were considered. Dispersion models included an embedded biological uptake model (BUM). Three types of BUMs were used: equilibrium, dynamic and allometric. Model results were compared with 137Cs measurements in water (surface, intermediate and deep layers), sediment and biota (zooplankton, non-piscivorous and piscivorous fish). A reasonable agreement in model/model and model/data comparisons was obtained.

Urinary Neutrophil Gelatinase-Associated Lipocalin as a Biomarker for Renal Injury in Liver Transplant Recipients Using Calcineurin Inhibitors.

BACKGROUND: Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is an early biomarker of renal injury. We examined the feasibility of using uNGAL as an early predictor of renal impairment in patients under calcineurin inhibitors in liver transplant recipients. METHODS: From urine samples obtained from liver transplant recipients, the glomerular filtration rate (GFR) at the time of urine sampling was compared with that at 5 to 7 months later. Patients were divided into 3 groups according to initial GFR and then divided into 2 groups according to the uNGAL level of 25 ng/mL. Progression of renal injury (PRI) was defined as a decrease in the GFR of more than 5 mL/min/1.73 m2 in the mild or moderate groups, or if a normal group patient shifted to the mild or moderate group. RESULTS: Fifty-one patients were enrolled. The mean uNGAL level was higher in the moderate group than in the normal and mild groups (18.38 ± 14.31 vs 7.74 ± 8.13; P < .01). A proportion of uNGAL-high was also higher in the moderate group than in the mild group (40% vs 5%; P = .03). uNGAL-high was a risk factor for 6-month PRI (odds ratio, 60.375; 95% confidence interval, 1.283-4088.25; P = .037) and 1-year PRI (odds ratio, 21.311; % confidence interval, 0.947-479.578; P = .054). CONCLUSIONS: A uNGAL of >25 ng/mg can be a marker for moderate renal impairment (GFR of 30-59 mL/min/1.73 m2) and a predictor of PRI at 6 months in patients using calcineurin inhibitors. Renal protection strategies should be considered in liver transplant recipients with a uNGAL of >25 ng/mg in spot urine sampling.

Challenging Alveolar Hemorrhage Complicating Pneumonia After Liver Transplantation: A Case Report.

Alveolar hemorrhage is a life-threatening clinical syndrome often initially thought to be atypical pneumonia. Association with hematopoietic stem cell transplantation is well studied, but not with solid organ transplantation. We report a case of a 54-year-old woman presented with fever and shortness of breath on the third posttransplant day after deceased donor liver transplantation. Imaging studies showed diffuse bilateral pulmonary infiltrates and a positive sequential bronchoalveolar lavage test was revealed during bronchoscopy. Cytomegalovirus antigenemia was present in 8/200,000 white blood cells; Aspergillus galactomannan and Pneumocystis jirovecii were also present. However, only Aspergillus hyphae were found in the sputum culture. Management strategy aimed to treat underlying infections, provide adequate respiratory support, and control inflammation. We proposed that diffuse alveolar hemorrhage should be considered as differential diagnosis in early pulmonary complications after liver transplantation. Early diagnosis and aggressive treatment protocol is the key for a good outcome.

Initial experience with purely laparoscopic living-donor right hepatectomy.

BACKGROUND: There may be concerns about purely laparoscopic donor right hepatectomy (PLDRH) compared with open donor right hepatectomy, especially when performed by surgeons accustomed to open surgery. This study aimed to describe technical tips and pitfalls in PLDRH. METHODS: Data from donors who underwent PLDRH at Seoul National University Hospital between December 2015 and July 2017 were analysed retrospectively. Endpoints analysed included intraoperative events and postoperative complications. All operations were performed by a single surgeon with considerable experience in open living donor hepatectomy. RESULTS: A total of 26 donors underwent purely laparoscopic right hepatectomy in the study interval. No donor required transfusion during surgery, whereas two underwent reoperation. In two donors, the dissection plane at the right upper deep portion of the midplane was not correct. One donor experienced portal vein injury during caudate lobe transection, and one developed remnant left hepatic duct stenosis. One donor experienced remnant portal vein angulation owing to a different approach angle, and one experienced arterial damage associated with the use of a laparoscopic energy device. One donor had postoperative bleeding due to masking of potential bleeding foci owing to intra-abdominal pressure during laparoscopy. Two donors experienced right liver surface damage caused by a xiphoid trocar. CONCLUSION: Purely laparoscopic donor hepatectomy differs from open donor hepatectomy in terms of angle and caudal view. Therefore, surgeons experienced in open donor hepatectomy must gain adequate experience in laparoscopic liver surgery and make adjustments when performing PLDRH.

Pure laparoscopic living donor hepatectomy: Focus on 55 donors undergoing right hepatectomy.

Although laparoscopic donor hepatectomy is increasingly common, few centers with substantial experience have reported the results of pure laparoscopic donor right hepatectomy (PLDRH). Here, we report the experiences of 60 consecutive liver donors undergoing pure laparoscopic donor hepatectomy (PLDH), with most undergoing right hepatectomy. None of the 60 donors who underwent PLDH had intraoperative complications and none required transfusions, reoperation, or conversion to open hepatectomy. Forty-five donors who underwent PLDRH between November 2015 and December 2016 were compared with 42 who underwent conventional donor right hepatectomy (CDRH) between May 2013 and February 2014. The total operation time was longer (330.7 vs 280.0 minutes; P < .001) and the percentage with multiple bile duct openings was higher (53.3% vs 26.2%; P = .010) in the PLDRH group. However, the length of postoperative hospital stay (8.4 vs 8.2 days; P = .495) and rate of complications (11.9% vs 8.9%; P = .733) and re-hospitalizations (4.8% vs 4.4%; P = 1.000) were similar in both groups. PLDH, including PLDRH, is feasible when performed by a highly experienced surgeon and transplant team. Further evaluation, including long-term results, may support these preliminary findings of comparative outcomes for donors undergoing PLDRH and CDRH.

Efficacy and Safety of Generic Mycophenolate Mofetil (My-rept) 500-Milligram Tablets in Primary Liver Transplant Recipients.

BACKGROUND: Generic immunosuppressants may be cost-effective if clinical outcomes are equivalent to the brand-name medications. Mycophenolate mofetil in the form of My-rept may be cost-effective being a generic immunosuppressant, which is available as a 500-mg tablet as well as a 250-mg capsule (Chong Kun Dang Pharmaceutical Corporation, Seoul, Korea). OBJECTIVE: This study aimed to evaluate the efficacy, safety, cost-effectiveness, and convenience of My-rept 500-mg tablets in liver transplant recipients. SETTING: The setting was an outpatient liver transplantation clinic of a tertiary hospital in Korea. METHOD: A phase 4, single-center, open-label, noncomparative study was undertaken. A total of 50 patients were recruited. Acute transplant rejection, changes in blood chemistry, white blood cell count, assessments of renal function, occurrence of adverse drug reactions, and other characteristics of the patients were recorded for 24 weeks. After study termination, a satisfaction survey was conducted. RESULTS: All enrolled patients and their liver grafts had survived for 24 weeks post-transplantation. No episodes of acute rejection were reported. Nine patients (18.8%) presented with adverse drug reactions that had been commonly reported with the use of other mycophenolate mofetil products, and no serious adverse drug reactions were reported. CONCLUSION: In conclusion, the My-rept 500-mg tablet appears to be feasible and convenient for administration to recipients of a liver transplant.

Primary Living-donor Liver Transplantation Is Not the Optimal Treatment Choice in Patients With Early Hepatocellular Carcinoma With Poor Tumor Biology.

OBJECTIVE: Liver resection (LR) and living-donor liver transplantation (LDLT) are considered the two potentially curative treatments for hepatocellular carcinoma (HCC). The aim of this study was to investigate whether there is a difference in the oncologic outcomes between LR and LDLT according to tumor biology. METHODS: Patients (137 LDLTs and 199 LRs) were stratified into four groups by tumor biology according to the number of risk factors for recurrence (preoperative alpha-fetoprotein >200 ng/mL, Edmonson grade 3 or 4, tumor size >3 cm, and presence of microvascular invasion). RESULTS: In the favorable tumor biology patients (groups I and II), there was a significantly worse recurrence-free survival rate in those patients who underwent LR compared to those who underwent LDLT (group I, P = .002; group II, P = .001). The overall survival rates in the LR and LDLT groups were not different (group I, P = .798; group II, P = .981). In the poor tumor biology patients (groups III and IV), there was no significant difference between the two groups in terms of recurrence-free survival rate (group III, P = .342; group IV, P = .616). The LDLT group showed a significantly lower overall survival rate (group III, P = .001; group IV, P = .025). CONCLUSIONS: Primary LDLT should not be recommended in early stage HCC patients with poor tumor biology because of lower survival rates and a high chance of HCC recurrence.

Usefulness of PIVKA-II After Living-donor Liver Transplantation for Hepatocellular Carcinoma.

OBJECTIVE: Prothrombin induced by the absence of vitamin K or antagonist-II (PIVKA-II) is a useful tumor marker for hepatocellular carcinoma (HCC). However, the usefulness of post-transplantation surveillance with PIVKA-II is not clear. We evaluated the clinical value of PIVKA-II in monitoring HCC recurrence after living-donor liver transplantation (LDLT). METHODS: One hundred twenty patients who had undergone LDLT for HCC from February 1999 to December 2010 and whose serum alpha-fetoprotein (AFP) and PIVKA-II had been measured sequentially before and after LDLT were included in this study. Patients were classified into four groups according to the preoperative level of AFP and PIVKA-II (group I, normal AFP and PIVKA-II; group II, elevated AFP; group III, elevated PIVKA-II; and group IV, elevated both AFP and PIVKA-II). RESULTS: Preoperative PIVKA-II level tended to increase with increasing tumor size, number of nodules, presence of microvascular invasion, and poor differentiation. In 27 patients developing recurrent HCC after LDLT, the sensitivity of AFP and PIVKA-II was 59.2% and 88.8%, respectively. When the two markers were combined, the sensitivity increased to 92.5%. Especially, the sensitivity for PIVKA-II was high at groups I and III (100.0% for both, respectively). In patients in groups I, III, and IV, an elevated PIVKA-II level was the most common first sign of HCC recurrence after LDLT. An elevated PIVKA-II level was the most common first sign of recurrence, regardless of recurrence site. CONCLUSIONS: PIVKA-II might be a useful tumor marker in the monitoring of recurrence after LDLT, complementary to AFP.

Surgical Techniques of Allogeneic Liver Transplantation in a Nonhuman Primate Model.

Herein, we report our experience of performing allogeneic orthotopic liver transplantation (LT) in nonhuman primates. We designed an allogeneic ABO-compatible orthotopic LT model in monkeys in a manner similar to that used in humans. We applied almost the same surgical procedures used for human conventional deceased donor LT. A total of 6 monkeys underwent allogeneic LT. One cynomolgus monkey aged 45 months (3.4 kg) and 5 rhesus macaque monkeys aged 50.2 ± 14.8 months (5.40 ± 0.33 kg) were used as recipients. In the donor surgery, the liver was perfused in situ through the aorta using cold histidine-tryptophan-ketoglutarate solution. The portal vein (diameter, 5-10 mm), supra- and infra-hepatic inferior vena cava (IVC) (diameter, 12-15 mm), and common bile duct (diameter, 1.5-3.0 mm) were dissected out. The hepatic artery was kept in continuity with the celiac trunk and abdominal aorta up to the iliac bifurcation (diameter, 5-6 mm). The mean graft weight was 102.0 g (94.8-111.0 g). Recipient surgery was conducted in parallel. After recipient hepatectomy, the graft was implanted. The suprahepatic IVC and portal vein were anastomosed to those of the graft. After reperfusion, the infrahepatic IVC was anastomosed. The aorta conduit of the graft was anastomosed to the infrarenal aorta of the recipient in a retrocolic end-to-side manner. Biliary reconstruction was performed in a duct-to-duct anastomosis with cholecystectomy. Mean operative time was 107.0 minutes for donor and 198.2 minutes for recipient. There was one operative death due to unknown cause. In conclusion, for allogeneic orthotopic LT in nonhuman primate model, we can apply almost the same procedure used for human conventional deceased donor LT in a similar manner.

Survival benefit of liver resection for Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma.

BACKGROUND: Although transarterial chemoembolization is recommended as the standard treatment for Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma (BCLC-B HCC), other treatments including liver resection have been used. This study aimed to determine the survival benefit of treatment strategies including resection for BCLC-B HCC compared with non-surgical treatments. METHODS: The nationwide multicentre database of the Korean Liver Cancer Association was reviewed. Patients with BCLC-B HCC who underwent liver resection as a first or second treatment within 2 years of diagnosis and patients who received non-surgical treatment were selected randomly. Survival outcomes of propensity score-matched groups were compared. RESULTS: Among 887 randomly selected patients with BCLC-B HCC, 83 underwent liver resection as first or second treatment and 597 had non-surgical treatment. After propensity score matching, the two groups were well balanced (80 patients in each group). Overall median survival in the resection group was better than that for patients receiving non-surgical treatment (50·9 versus 22·1 months respectively; P < 0·001). The 1-, 2-, 3- and 5-year overall survival rates in the resection group were 90, 88, 75 and 63 per cent, compared with 79, 48, 35 and 22 per cent in the no-surgery group (P < 0·001). In multivariable analysis, non-surgical treatment only (hazard ratio (HR) 3·35, 95 per cent c.i. 2·16 to 5·19; P < 0·001), albumin level below 3·5 g/dl (HR 1·96, 1·22 to 3·15; P = 0·005) and largest tumour size greater than 5·0 cm (HR 1·81, 1·20 to 2·75; P = 0·005) were independent predictors of worse overall survival. CONCLUSION: Treatment strategies that include liver resection offer a survival benefit compared with non-surgical treatments for potentially resectable BCLC-B HCC.

Modelling of marine radionuclide dispersion in IAEA MODARIA program: Lessons learnt from the Baltic Sea and Fukushima scenarios.

State-of-the art dispersion models were applied to simulate (137)Cs dispersion from Chernobyl nuclear power plant disaster fallout in the Baltic Sea and from Fukushima Daiichi nuclear plant releases in the Pacific Ocean after the 2011 tsunami. Models were of different nature, from box to full three-dimensional models, and included water/sediment interactions. Agreement between models was very good in the Baltic. In the case of Fukushima, results from models could be considered to be in acceptable agreement only after a model harmonization process consisting of using exactly the same forcing (water circulation and parameters) in all models. It was found that the dynamics of the considered system (magnitude and variability of currents) was essential in obtaining a good agreement between models. The difficulties in developing operative models for decision-making support in these dynamic environments were highlighted. Three stages which should be considered after an emergency, each of them requiring specific modelling approaches, have been defined. They are the emergency, the post-emergency and the long-term phases.

Malignant mesonephric tumor of the cervix with an initial manifestation as pulmonary metastasis: case report and review of the literature.

Malignant mesonephric tumor (MMT) is a relatively uncommon malignancy of the female genital tract. The diagnosis of metastatic MMT is difficult because cytological, pathological, immunohistochemical characteristics of MMT are under-recognized. The authors present a 55-year-old female with metastatic pulmonary nodules. The bronchial washing cytology revealed three dimensional clusters of bland epithelial cells with slight nuclear grooves. A corresponding lung histology had ductal or tubular clusters of epithelial cells with intraglandular eosinophilic materials. These epithelial cells were positive for immunohistochemical stain of CD10, suggesting metastasis from MMT. The cervical smear showed clusters of bland, gland-forming epithelial cells with intraglandular eosinophilic materials. On histologic examination, mesonephric adenocarcinoma with papillary and solid proliferation was identified in the uterine cervix. A review of the literature for 72 cases of MMT is also included. Clinical and cytopathological features of MMT are herein made available.

Beneficial Effects of Necrosis Modulator, Indole Derivative NecroX-7, on Renal Ischemia-Reperfusion Injury in Rats.

Renal ischemia-reperfusion injury (IRI) is involved in multiple diseases, such as kidney transplantation or contrast-induced nephropathy, and leads to acute kidney injury. However, there are no pharmacological agents available to prevent IRI. In this study, we investigated the effects of necroX-7 against renal IRI in a rat model. Seven-week-old male Sprague-Dawley rats were divided into four groups: saline-treated sham or IRI group, necroX-7-treated sham or IRI group. All animals had right nephrectomy and IRI was followed by reperfusion after clamping the left renal vessels for 35 minutes. NecroX-7 or saline was intravenously injected at 5 minutes before reperfusion. The effects of necroX-7 on IRI were evaluated using biochemical, histological, and molecular markers. The serum creatinine level was increased after IRI compared with sham. The necroX-7 significantly decreased creatinine level compared with the saline in IRI (1.36 ± 0.11 vs 2.35 ± 0.42 mg/dL; P < .05). An immunohistochemical study revealed that necroX-7 improved renal tubular injury, and attenuated 8-OHdG-positive cells (P < .001) and high-mobility group Box 1 protein (HMGB1) expression compared with saline treatment in IRI (P < .001). NecroX-7 significantly reduced monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor (TNF)-α, and interleukin (IL)-1ß in IRI (necroX-7-treated IRI vs saline-treated IRI rats; 1.73 ± 0.42 vs 7.23 ± 0.54-fold for MCP-1, P < .05; 0.79 ± 0.59 vs 3.72 ± 0.37-fold for TNF-α, P < .05; 0.50 ± 0.36 vs 2.43 ± 0.41-fold for IL-1ß, P < .001). In conclusion, necroX-7 improved renal dysfunction after IRI. These effects of necroX-7 occurred with the suppression of reactive oxygen species, HMGB1, and inflammatory responses. We suggest that necroX-7 has potential therapeutic benefits in renal IRI.

Inter-comparison of dynamic models for radionuclide transfer to marine biota in a Fukushima accident scenario.

We report an inter-comparison of eight models designed to predict the radiological exposure of radionuclides in marine biota. The models were required to simulate dynamically the uptake and turnover of radionuclides by marine organisms. Model predictions of radionuclide uptake and turnover using kinetic calculations based on biological half-life (TB1/2) and/or more complex metabolic modelling approaches were used to predict activity concentrations and, consequently, dose rates of (90)Sr, (131)I and (137)Cs to fish, crustaceans, macroalgae and molluscs under circumstances where the water concentrations are changing with time. For comparison, the ERICA Tool, a model commonly used in environmental assessment, and which uses equilibrium concentration ratios, was also used. As input to the models we used hydrodynamic forecasts of water and sediment activity concentrations using a simulated scenario reflecting the Fukushima accident releases. Although model variability is important, the intercomparison gives logical results, in that the dynamic models predict consistently a pattern of delayed rise of activity concentration in biota and slow decline instead of the instantaneous equilibrium with the activity concentration in seawater predicted by the ERICA Tool. The differences between ERICA and the dynamic models increase the shorter the TB1/2 becomes; however, there is significant variability between models, underpinned by parameter and methodological differences between them. The need to validate the dynamic models used in this intercomparison has been highlighted, particularly in regards to optimisation of the model biokinetic parameters.