[Transplantation for acute-on-chronic liver failure]. / Transplantation beim akut-auf-chronischen Leberversagen.

A review and discussion of the current literature on liver transplantation for acute-on-chronic liver failure (ACLF) was performed. The ACLF represents an acute deterioration of liver function with pre-existing liver disease and is associated with increasing multiorgan failure, depending on the stage. The 28-day mortality ranges to well over 70% in stage 3 and requires rapid intensive medical treatment involving an interdisciplinary team experienced in transplantation medicine. Under optimized conditions, liver transplantation provides long-term survival rates comparable to other indications. Achieving this requires a differentiated donor selection, choosing the appropriate time for transplantation in the context of a dynamic disease course and the use of appropriate surgical techniques.

Prediction of key milk biomarkers in dairy cows through milk mid-infrared spectra and international collaborations.

At the individual cow level, suboptimum fertility, mastitis, negative energy balance, and ketosis are major issues in dairy farming. These problems are widespread on dairy farms and have an important economic impact. The objectives of this study were (1) to assess the potential of milk mid-infrared (MIR) spectra to predict key biomarkers of energy deficit (citrate, isocitrate, glucose-6 phosphate [glucose-6P], free glucose), ketosis (ß-hydroxybutyrate [BHB] and acetone), mastitis (N-acetyl-ß-d-glucosaminidase activity [NAGase] and lactate dehydrogenase), and fertility (progesterone); (2) to test alternative methodologies to partial least squares (PLS) regression to better account for the specific asymmetric distribution of the biomarkers; and (3) to create robust models by merging large datasets from 5 international or national projects. Benefiting from this international collaboration, the dataset comprised a total of 9,143 milk samples from 3,758 cows located in 589 herds across 10 countries and represented 7 breeds. The samples were analyzed by reference chemistry for biomarker contents, whereas the MIR analyses were performed on 30 instruments from different models and brands, with spectra harmonized into a common format. Four quantitative methodologies were evaluated to address the strongly skewed distribution of some biomarkers. Partial least squares regression was used as the reference basis, and compared with a random modification of distribution associated with PLS (random-downsampling-PLS), an optimized modification of distribution associated with PLS (KennardStone-downsampling-PLS), and support vector machine (SVM). When the ability of MIR to predict biomarkers was too low for quantification, different qualitative methodologies were tested to discriminate low versus high values of biomarkers. For each biomarker, 20% of the herds were randomly removed within all countries to be used as the validation dataset. The remaining 80% of herds were used as the calibration dataset. In calibration, the 3 alternative methodologies outperform the PLS performances for the majority of biomarkers. However, in the external herd validation, PLS provided the best results for isocitrate, glucose-6P, free glucose, and lactate dehydrogenase (coefficient of determination in external herd validation [R2v] = 0.48, 0.58, 0.28, and 0.24, respectively). For other molecules, PLS-random-downsampling and PLS-KennardStone-downsampling outperformed PLS in the majority of cases, but the best results were provided by SVM for citrate, BHB, acetone, NAGase, and progesterone (R2v = 0.94, 0.58, 0.76, 0.68, and 0.15, respectively). Hence, PLS and SVM based on the entire dataset provided the best results for normal and skewed distributions, respectively. Complementary to the quantitative methods, the qualitative discriminant models enabled the discrimination of high and low values for BHB, acetone, and NAGase with a global accuracy around 90%, and glucose-6P with an accuracy of 83%. In conclusion, MIR spectra of milk can enable quantitative screening of citrate as a biomarker of energy deficit and discrimination of low and high values of BHB, acetone, and NAGase, as biomarkers of ketosis and mastitis. Finally, progesterone could not be predicted with sufficient accuracy from milk MIR spectra to be further considered. Consequently, MIR spectrometry can bring valuable information regarding the occurrence of energy deficit, ketosis, and mastitis in dairy cows, which in turn have major influences on their fertility and survival.

ON THE PLACEMENT OF APRON DOSEMETERS AND DOSE ASSESSMENT IN INTERVENTIONAL CARDIOLOGY PROCEDURES: PRELIMINARY RESULTS.

Personnel involved in interventional practices are likely to be exposed to higher radiation doses than other workers in the medical field. Personnel monitoring and radiation protection measures play a crucial role in keeping these doses below the limits. EURADOS (European Radiation Dosimetry Group) Working Group 12 performed a series of investigations showing how the complexity of the scattered field reaching the operators can influence the doses to the operators. The present work was aimed at determining the possible effects on the registered doses of the scattered field and the actual position of a dosemeter on apron. This study has been performed through Monte Carlo simulations and it was validated through measurements. It does not claim to identify the 'best' position for the dosemeter, but to assess the variability of its response, showing how a variability of the order of +/- 30% to 40 should be taken into account.

On the complexity of predicting tablet capping.

Predicting tablet defects, such as capping, that might occur during manufacturing, is a challenge in the pharmaceutical industry. In the literature, different parameters were presented to predict capping but no general consensus seems to have been reached yet. In this article, we chose to study a wide range of products (18 formulations, 8 of which presenting capping) to predict capping on biconvex tablets using the properties characterized on defect-free flat-faced tablets (tensile strength, solid fraction, elastic recovery, etc.), made using the same process parameters. Single parameters and predictive indices presented in the literature were evaluated on this set of formulations and were found not suitable to predict capping. A predictive model was then developed using a decision tree analysis and was found to depend only on three in-die tablet properties: the plastic energy per volume, the in-die elastic recovery and the residual die-wall pressure. This model was tested on another set of 13 formulations chosen to challenge it. The capping behavior of 29 out of the 31 formulations studied in total was well estimated using the developed model with only two products which were predicted to cap and did not. This shows the potential of the used approach in terms of risk analysis and assessment for capping occurrence.

Impact of unloading kinematics on the occurrence of capping during the production of pharmaceutical tablets.

Capping is a common defect that can occur during the manufacturing of pharmaceutical tablets. Several studies showed that decreasing the unloading speed of the manufacturing cycle plays a role in the occurrence of such defects. Following this idea, we study in this work the influence of the unloading step on capping using a compaction simulator. Measuring the die wall pressure made it possible to detect precisely that tablets capped just after the unloading (some milliseconds only). To evaluate the impact of the unloading speed on capping, we developed a two-step unloading phase controlled by three manufacturing parameters. It was possible to mitigate capping by decreasing the speed at which the contact between the punches and the tablet was lost. Capping seemed due to dynamical effects related to the release of the axial pressure. The modification of the unloading step to mitigate capping led to significant changes in tablet density but no clear trends were found for the residual die-wall pressure and tablet strength. This work made it possible to improve the understanding of capping. Moreover, the two-step unloading cycle gave a new idea for possible modifications that could be done on rotary presses in order to mitigate capping.

Pancreatic Fistula and Biochemical Leak after Splenectomy: Incidence and Risk Factors-A Retrospective Single-Center Analysis.

PURPOSE: Postoperative pancreatic fistula (POPF) is a complication discussed in the context of pancreatic surgery, but may also result from splenectomy; a relationship that has not been investigated extensively yet. METHODS: This retrospective single-center study aimed to analyze incidence of and risk factors for POPF after splenectomy. Patient characteristics included demographic data, surgical procedure, and intra- and postoperative complications. POPF was defined according to the International Study Group on Pancreatic Surgery as POPF of grade B and C or biochemical leak (BL). RESULTS: Over ten years, 247 patients were identified, of whom 163 underwent primary (spleen-associated pathologies) and 84 secondary (extrasplenic oncological or technical reasons) splenectomy. Thirty-six patients (14.6%) developed POPF of grade B/C or BL, of which 13 occurred after primary (7.9%) and 23 after secondary splenectomy (27.3%). Of these, 25 (69.4%) were BL, 7 (19.4%) POPF of grade B and 4 (11.1%) POPF of grade C. BL were treated conservatively while three patients with POPF of grade B required interventional procedures and 4 with POPF of grade C required surgery. POPF and BL was noted significantly more often after secondary splenectomy and longer procedures. Multivariate analysis confirmed secondary splenectomy and use of energy-based devices as independent risk factors for development of POPF/BL after splenectomy. CONCLUSION: With an incidence of 4.5%, POPF is a relevant complication after splenectomy. The main risk factor identified was secondary splenectomy. Although POPF and BL can usually be treated conservatively, it should be emphasized when obtaining patients' informed consent and treated at centers with experience in pancreatic surgery.

Tracking the source of contaminant lead in children's blood.

Pb isotope ratios are used for apportioning the sources of Pb in the blood of children (ages 1-6) screened for high blood Pb levels (>5 µg/dL) surrounding urban areas of Kansas City, MO. We compared Pb isotope ratios measured in the child's blood with those of the most likely sources of Pb in that child's home environment. The environmental sources sampled consisted of topsoils, paints, occupational sources (e.g., oil rig workers' uniforms, mechanics' clothes), indoor air filters, dusts, and dietary sources (e.g., spices). Blood lead levels (BLL) ranged from 2.9 to 12.7 µg/dL in children from the five homes participating in this study. Measurements of 206Pb/204Pb, 207Pb/204Pb and 208Pb/204Pb isotope ratios were made by multi-collector ICP-MS. Comparison of the Pb isotope ratios in home environment samples versus those in the child's blood in each home allowed the identification of possible sources of a child's Pb exposure in three homes. In five homes investigated, children's blood Pb levels were most likely to be derived from dusts inside, and topsoil outside, the homes, or a mixture thereof. In one case, blood Pb was derived from turmeric spice and, in another, the Pb was derived from paint. It is not always possible to directly link high BLLs to the environmental sources collected when Pb isotope ratios of the environmental samples did not overlap with those of the blood.

Characterization of the viscoelasticity of pharmaceutical tablets using impulse excitation technique.

Pharmaceutical tablets can be produced on different kinds of presses that may have very different compaction kinematics. Strain rate sensitivity (SRS) is thus an important property for the powders used to produce pharmaceutical tablets. Viscoelasticity is one of the aspects of the SRS and can be sometimes difficult to characterize. In this work, impulse excitation technique was used as an easy-to-implement method for characterizing viscoelasticity using the fact that this property induces damping which can be detected on resonance spectra as peak enlargements. A damping ratio, related to the first flexural vibration mode, was determined on impulse excitation frequency spectra using the half-power bandwidth method on tablets made with different products. This method made it possible to obtain reproducible results for the damping ratio. As viscoelasticity is not the only phenomena that can promote damping, tests were made in order to assess the influence of other parameters: viscoplasticity, porosity and tablet dimensions. Results indicated that the influence of these phenomena could be considered as negligible. Finally, the damping ratios determined were in good accordance with the known viscoelastic behavior of the studied products. This made it possible to confirm that impact resonance is an easy and quick way to characterize the viscoelastic nature of pharmaceutical tablets.

Use of impulse excitation technique for the characterization of the elastic anisotropy of pharmaceutical tablets.

Capping and lamination are common defects occurring during the manufacturing of pharmaceutical tablets. Several studies showed that tablet anisotropy can play a role in the occurrence of such defects. In this work, we propose a new and easy methodology to characterize the anisotropy of flat-faced cylindrical tablets, which are considered as transversally isotropic due to the process, through the study of their elastic properties using impulse excitation technique and finite-element method (FEM) simulations. The study was performed for tablets with a thickness-to-diameter-ratio between 0.160 and 0.222. FEM simulations showed that it was possible to determine three out of the five elastic constants of the tablet using the first three natural vibration modes. An anisotropic index was then built as the ratio of the two apparent shear moduli. Moreover, in order to simplify the estimation of tablet anisotropy and to avoid the systematic use of FEM simulations, an analytical model was also developed. It only requires the measurement of the tablet dimensions and of the first three natural frequencies. Using this technique, experimental measurements on tablets made of classical pharmaceutical excipients were done and found coherent with the existing literature. This indicates thus that this methodology is a quick, easy and reliable characterization method in order to access tablet anisotropy.

Differences in net fat oxidation, heat production, and liver mitochondrial DNA copy numbers between high and low feed-efficient dairy cows.

Improving feed utilization efficiency in dairy cattle could have positive economic and environmental effects that would support the sustainability of the dairy industry. Identifying key differences in metabolism between high and low feed-efficient animals is vital to enhancing feed conversion efficiency. Therefore, our objectives were (1) to determine whether cows grouped by either high or low feed efficiency have measurable differences in net fat and carbohydrate metabolism that account for differences in heat production (HP), and if so, whether these differences also exists under conditions of feed withdrawal when the effect of feeding on HP is minimized, and (2) to determine whether the abundance of mitochondria in the liver can be related to the high or low feed-efficient groups. Ten dairy cows from a herd of 15 (parity = 2) were retrospectively grouped into either a high (H) or a low (L) feed-efficient group (n = 5 per group) based on weekly energy-corrected milk (ECM) divided by dry mater intake (DMI) from wk 4 through 30 of lactation. Livers were biopsied at wk -4, 2, and 12, and blood was sampled weekly from wk -3 to 12 relative to parturition. Blood was subset to be analyzed for the transition period (wk -3 to 3) and from wk 4 to 12. In wk 5.70 ± 0.82 (mean ± SD) postpartum (PP), cows spent 2 d in respiration chambers (RC), in which CO2, O2, and CH4 gases were measured every 6 min for 24 h. Fatty acid oxidation (FOX), carbohydrate oxidation (COX), metabolic respiratory quotient (RQ), and HP were calculated from gas measurements for 23 h. Cows were fed ad libitum (AD-LIB) on d 1 and had feed withdrawn (RES, restricted diet) on d 2. Additional blood samples were taken at the end of the AD-LIB and RES feeding periods in the RC. During wk 4 to 30 PP, H had greater DMI/kg of metabolic body weight (BW0.75), ECM per kilogram of BW0.75 yield, and ECM/DMI ratio, compared with L, but a lower body condition score between wk 4 and 12 PP. In the RC period, we detected no differences in BW, DMI, or milk yield between groups. We also detected no significant group or group by feeding period interactions for plasma metabolites except for Revised Quantitative Insulin Sensitivity Check Index, which tended to have a group by feeding period interaction. The H group had lower HP and HP per kilogram of BW0.75 compared with L. Additionally, H had lower FOX and FOX per kilogram of BW0.75 compared with L during the AD-LIB period. Methane, CH4 per kilogram of BW0.75, and CH4 per kilogram of milk yield were lower in H compared with L, but, when adjusted for DMI, CH4/DMI did not differ between groups, nor did HP/DMI. Relative mitochondrial DNA copy numbers in the liver were lower in the L than in the H group. These results suggest that lower feed efficiency in dairy cows may result from fewer mitochondria per liver cell as well as a greater whole-body HP, which likely partially results from higher net fat oxidation.

Relationships between metabolic profiles and gene expression in liver and leukocytes of dairy cows in early lactation.

Homeorhetic mechanisms assist dairy cows in the transition from pregnancy to lactation. Less successful cows develop severe negative energy balance (NEB), placing them at risk of metabolic and infectious diseases and reduced fertility. We have previously placed multiparous Holstein Friesian cows from 4 herds into metabolic clusters, using as biomarkers measurements of plasma nonesterified fatty acids, ß-hydroxybutyrate, glucose and IGF-1 collected at 14 and 35 d in milk (DIM). This study characterized the global transcriptomic profiles of liver and circulating leukocytes from the same animals to determine underlying mechanisms associated with their metabolic and immune function. Liver biopsy and whole-blood samples were collected around 14 DIM for RNA sequencing. All cows with available RNA sequencing data were placed into balanced (BAL, n = 44), intermediate (n = 44), or imbalanced (IMBAL, n = 19) metabolic cluster groups. Differential gene expression was compared between the 3 groups using ANOVA, but only the comparison between BAL and IMBAL cows is reported. Pathway analysis was undertaken using DAVID Bioinformatic Resources (https://david.ncifcrf.gov/). Milk yields did not differ between BAL and IMBAL cows but dry matter intake was less in IMBAL cows and they were in greater energy deficit at 14 DIM (-4.48 v -11.70 MJ/d for BAL and IMBAL cows). Significantly differentially expressed pathways in hepatic tissue included AMPK signaling, glucagon signaling, adipocytokine signaling, and insulin resistance. Genes involved in lipid metabolism and cholesterol transport were more highly expressed in IMBAL cows but IGF1 and IGFALS were downregulated. Leukocytes from BAL cows had greater expression of histones and genes involved in nucleosomes and cell division. Leukocyte expression of heat shock proteins increased in IMBAL cows, suggesting an unfolded protein response, and several key genes involved in immune responses to pathogens were upregulated (e.g., DEFB13, HP, OAS1Z, PTX3, and TLR4). Differentially expressed genes upregulated in IMBAL cows in both tissues included CD36, CPT1, KFL11, and PDK4, all central regulators of energy metabolism. The IMBAL cows therefore had greater difficulty maintaining glucose homeostasis and had dysregulated hepatic lipid metabolism. Their energy deficit was associated with a reduced capacity for cell division and greater evidence of stress responses in the leukocyte population, likely contributing to an increased risk of infectious disease.

[Machine perfusion for conditioning liver and kidneys before transplantation]. / Maschinenperfusion zur Konditionierung der Leber und Niere vor Transplantation.

Machine perfusion will become established as the standard of care for solid organ transplantation in the near future. Ongoing studies are investigating the appropriate perfusion algorithms for each specific organ. Although it is neither proven which perfusion principle nor type of device is superior, it has already been sufficiently shown that the increasing number of marginal organs that are currently transplanted in Germany would benefit from machine perfusion for conditioning before transplantation. The addition of hypothermic and normothermic perfusion sequences opens up the possibility of conditioning of previously damaged organs as well as viability testing. Overall, machine perfusion increases the safety for the recipient and can counteract the increasingly more difficult scenario of working hour restrictions because solid organ transplantations in the future will be plannable and carried out during the day.

Automatic recording of individual oestrus vocalisation in group-housed dairy cattle: development of a cattle call monitor.

Oestrus detection remains a problem in the dairy cattle industry. Therefore, automatic detection systems have been developed to detect specific behavioural changes at oestrus. Vocal behaviour has not been considered in such automatic oestrus detection systems in cattle, though the vocalisation rate is known to increase during oestrus. The main challenge in using vocalisation to detect oestrus is correctly identifying the calling individual when animals are moving freely in large groups, as oestrus needs to be detected at an individual level. Therefore, we aimed to automate vocalisation recording and caller identification in group-housed dairy cows. This paper first presents the details of such a system and then presents the results of a pilot study validating its functionality, in which the automatic detection of calls from individual heifers was compared to video-based assessment of these calls by a trained human observer, a technique that has, until now, been considered the 'gold standard'. We developed a collar-based cattle call monitor (CCM) with structure-borne and airborne sound microphones and a recording unit and developed a postprocessing algorithm to identify the caller by matching the information from both microphones. Five group-housed heifers, each in the perioestrus or oestrus period, were equipped with a CCM prototype for 5 days. The recorded audio data were subsequently analysed and compared with audiovisual recordings. Overall, 1404 vocalisations from the focus heifers and 721 vocalisations from group mates were obtained. Vocalisations during collar changes or malfunctions of the CCM were omitted from the evaluation. The results showed that the CCM had a sensitivity of 87% and a specificity of 94%. The negative and positive predictive values were 80% and 96%, respectively. These results show that the detection of individual vocalisations and the correct identification of callers are possible, even in freely moving group-housed cattle. The results are promising for the future use of vocalisation in automatic oestrus detection systems.

Between- and within-herd variation in blood and milk biomarkers in Holstein cows in early lactation.

Both blood- and milk-based biomarkers have been analysed for decades in research settings, although often only in one herd, and without focus on the variation in the biomarkers that are specifically related to herd or diet. Biomarkers can be used to detect physiological imbalance and disease risk and may have a role in precision livestock farming (PLF). For use in PLF, it is important to quantify normal variation in specific biomarkers and the source of this variation. The objective of this study was to estimate the between- and within-herd variation in a number of blood metabolites (ß-hydroxybutyrate (BHB), non-esterified fatty acids, glucose and serum IGF-1), milk metabolites (free glucose, glucose-6-phosphate, urea, isocitrate, BHB and uric acid), milk enzymes (lactate dehydrogenase and N-acetyl-ß-D-glucosaminidase (NAGase)) and composite indicators for metabolic imbalances (Physiological Imbalance-index and energy balance), to help facilitate their adoption within PLF. Blood and milk were sampled from 234 Holstein dairy cows from 6 experimental herds, each in a different European country, and offered a total of 10 different diets. Blood was sampled on 2 occasions at approximately 14 days-in-milk (DIM) and 35 DIM. Milk samples were collected twice weekly (in total 2750 samples) from DIM 1 to 50. Multilevel random regression models were used to estimate the variance components and to calculate the intraclass correlations (ICCs). The ICCs for the milk metabolites, when adjusted for parity and DIM at sampling, demonstrated that between 12% (glucose-6-phosphate) and 46% (urea) of the variation in the metabolites' levels could be associated with the herd-diet combination. Intraclass Correlations related to the herd-diet combination were generally higher for blood metabolites, from 17% (cholesterol) to approximately 46% (BHB and urea). The high ICCs for urea suggest that this biomarker can be used for monitoring on herd level. The low variance within cow for NAGase indicates that few samples would be needed to describe the status and potentially a general reference value could be used. The low ICC for most of the biomarkers and larger within cow variation emphasises that multiple samples would be needed - most likely on the individual cows - for making the biomarkers useful for monitoring. The majority of biomarkers were influenced by parity and DIM which indicate that these should be accounted for if the biomarker should be used for monitoring.

Continuous pH monitoring in wounds using a composite indicator dressing - A feasibility study.

PURPOSE: Modern burn care strives for new means to guarantee optimised wound healing. Several studies have shown a correlation between the pH value in a (burn) wound and successful wound healing. A multitude of devices to monitor pH is available, all requiring direct wound contact and removal of the dressing for pH monitoring. The aim of this feasibility study was to create a sterile and easy to handle method for pH monitoring while simultaneously using an advanced wound dressing. MATERIALS AND METHODS: Dressing sheets of biotechnologically generated nanofibrillar cellulose (epicitehydro) were chemically functionalised with the indicator dye GJM-534. pH-donors with increasing pH were subsequently applied to the created indicator dressing. To investigate temporal resolution and continuous monitoring we used circular pH-donors with different pH (7 and 10) and decreasing diameters that were placed on another dressing sheet. Clinically relevant spatial resolution was checked by a wound bed simulation with small areas (8 mm) of higher pH (10) on a field of lower pH (7) and vice versa. RESULTS: The indicator dressing showed a gradual colouring from yellow to dark orange with increasing pH in steps of 0.3. After conversion of digital pictures to greyscale values, a sigmoidal distribution with a pKa-value of 8.4 was obtained. A ring-like pattern with alternating colour change corresponding to the pH was observed in the continuous monitoring experiment and the wound bed simulation delivered excellent local resolution. CONCLUSION: Since the pH of a (burn) wound can have a significant influence on wound healing, a pH indicator was successfully linked to an advanced, temporary, alloplastic wound dressing material. We were able to show the possibility of pH monitoring by the dressing itself. Additional testing, including studies with large case numbers for optimisation are necessary before clinical implementation.

Dynamic gut microbiome changes following regional intestinal lymphatic obstruction in primates.

The pathogenesis of inflammatory bowel disease (IBD) has been linked with lymphostasis, but whether and how lymphatic obstruction might disturb the intestinal microbiome in the setting of Crohn's Disease (CD) is currently unknown. We employed a new model of CD in African Green monkeys, termed 'ATLAS' (African green monkey truncation of lymphatics with obstruction and sclerosis), to evaluate how gut lymphatic obstruction alters the intestinal microbiome at 7, 21 and 61 days. Remarkable changes in several microbial sub- groupings within the gut microbiome were observed at 7 days post-ATLAS compared to controls including increased abundance of Prevotellaceae and Bacteroidetes-Prevotella-Porphyromonas (BPP), which may contribute to disease activity in this model of gut injury. To the best of our knowledge, these findings represent the first report linking lymphatic structural/gut functional changes with alterations in the gut microbiome as they may relate to the pathophysiology of CD.

Simulation of H p (10) and effective dose received by the medical staff in interventional radiology procedures.

Interventional radiology and cardiology are widespread employed techniques for diagnosis and treatment of several pathologies because they avoid the majority of the side-effects associated with surgical treatments, but are known to increase the radiation exposure to patient and operators. In recent years many studies treated the exposure of the operators performing cardiological procedures. The aim of this work is to study the exposure condition of the medical staff in some selected interventional radiology procedures. The Monte Carlo simulations have been employed with anthropomorphic mathematical phantoms reproducing the irradiation scenario of the medical staff with two operators and the patient. A personal dosemeter, put on apron, was modelled for comparison with measurements performed in hospitals, done with electronic dosemeters, in a reduced number of interventional radiology practices. Within the limits associated to the use of numerical anthropomorphic models to mimic a complex interventional procedure, the personal dose equivalent, H p (10), was evaluated and normalised to the simulated Kerma-Area Product, KAP, value, indeed the effective dose has been calculated. The H p (10)/KAPvalue of the first operator is about 10 µSv/Gy.cm2, when ceiling shielding is not used. This value is calculated on the trunk and it varies of +/-30% moving the dosemeter to the waist or to the neck. The effective dose, normalised to the KAP value, varies between 0.03 and 0.4 µSv/Gy.cm2. Considering all the unavoidable approximation of this kind of investigations, the comparisons with hospital measurement and literature data showed a good agreement allowing to use of the present results for dosimetric characterisation of interventional radiology procedures.

Potential of milk mid-IR spectra to predict metabolic status of cows through blood components and an innovative clustering approach.

Unbalanced metabolic status in the weeks after calving predisposes dairy cows to metabolic and infectious diseases. Blood glucose, IGF-I, non-esterified fatty acids (NEFA) and ß-hydroxybutyrate (BHB) are used as indicators of the metabolic status of cows. This work aims to (1) evaluate the potential of milk mid-IR spectra to predict these blood components individually and (2) to evaluate the possibility of predicting the metabolic status of cows based on the clustering of these blood components. Blood samples were collected from 241 Holstein cows on six experimental farms, at days 14 and 35 after calving. Blood samples were analyzed by reference analysis and metabolic status was defined by k-means clustering (k=3) based on the four blood components. Milk mid-IR analyses were undertaken on different instruments and the spectra were harmonized into a common standardized format. Quantitative models predicting blood components were developed using partial least squares regression and discriminant models aiming to differentiate the metabolic status were developed with partial least squares discriminant analysis. Cross-validations were performed for both quantitative and discriminant models using four subsets randomly constituted. Blood glucose, IGF-I, NEFA and BHB were predicted with respective R 2 of calibration of 0.55, 0.69, 0.49 and 0.77, and R 2 of cross-validation of 0.44, 0.61, 0.39 and 0.70. Although these models were not able to provide precise quantitative values, they allow for screening of individual milk samples for high or low values. The clustering methodology led to the sharing out of the data set into three groups of cows representing healthy, moderately impacted and imbalanced metabolic status. The discriminant models allow to fairly classify the three groups, with a global percentage of correct classification up to 74%. When discriminating the cows with imbalanced metabolic status from cows with healthy and moderately impacted metabolic status, the models were able to distinguish imbalanced group with a global percentage of correct classification up to 92%. The performances were satisfactory considering the variables are not present in milk, and consequently predicted indirectly. This work showed the potential of milk mid-IR analysis to provide new metabolic status indicators based on individual blood components or a combination of these variables into a global status. Models have been developed within a standardized spectral format, and although robustness should preferably be improved with additional data integrating different geographic regions, diets and breeds, they constitute rapid, cost-effective and large-scale tools for management and breeding of dairy cows.

Replacing the Draize eye test: Impedance spectroscopy as a 3R method to discriminate between all GHS categories for eye irritation.

Highly invasive animal based test procedures for risk assessment such as the Draize eye test are under increasing criticism due to poor transferability for the human organism and animal-welfare concerns. However, besides all efforts, the Draize eye test is still not completely replaced by alternative animal-free methods. To develop an in vitro test to identify all categories of eye irritation, we combined organotypic cornea models based on primary human cells with an electrical readout system that measures the impedance of the test models. First, we showed that employing a primary human cornea epithelial cell based model is advantageous in native marker expression to the primary human epidermal keratinocytes derived models. Secondly, by employing a non-destructive measuring system based on impedance spectroscopy, we could increase the sensitivity of the test system. Thereby, all globally harmonized systems categories of eye irritation could be identified by repeated measurements over a period of 7 days. Based on a novel prediction model we achieved an accuracy of 78% with a reproducibility of 88.9% to determine all three categories of eye irritation in one single test. This could pave the way according to the 3R principle to replace the Draize eye test.