Artificial soil (AS) is used in soil ecotoxicology as a test medium or reference matrix. AS is prepared according to standard OECD/ISO protocols and components of local sources are usually used by laboratories. This may result in significant inter-laboratory variations in AS properties and, consequently, in the fate and bioavailability of tested chemicals. In order to reveal the extent and sources of variations, the batch equilibrium method was applied to measure the sorption of 2 model compounds (phenanthrene and cadmium) to 21 artificial soils from different laboratories. The distribution coefficients (Kd) of phenanthrene and cadmium varied over one order of magnitude: from 5.3 to 61.5L/kg for phenanthrene and from 17.9 to 190L/kg for cadmium. Variations in phenanthrene sorption could not be reliably explained by measured soil properties; not even by the total organic carbon (TOC) content which was expected. Cadmium logKd values significantly correlated with cation exchange capacity (CEC), pHH2O and pHKCl, with Pearson correlation coefficients of 0.62, 0.80, and 0.79, respectively. CEC and pHH2O together were able to explain 72% of cadmium logKd variability in the following model: logKd=0.29pHH2O+0.0032 CEC -0.53. Similarly, 66% of cadmium logKd variability could be explained by CEC and pHKCl in the model: logKd=0.27pHKCl+0.0028 CEC -0.23. Variable cadmium sorption in differing ASs could be partially treated with these models. However, considering the unpredictable variability of phenanthrene sorption, a more reliable solution for reducing the variability of ASs from different laboratories would be better harmonization of AS preparation and composition.
For n-butanol production by Clostridium pasteurianum DSM 525, a modified reinforced Clostridium medium was used, where glucose was alternated with glycerol and two kinds of continuous fermentation were tested using suspended and surface immobilized cells on corn stover pieces. A steady state, with butanol productivity of 4.2g/Lh, was reached during the packed-bed continuous fermentation at a dilution rate of 0.44h(-1). The average n-butanol concentration, yield and the ratio of n-butanol/liquid by-products were 10.4g/L, 33 % and 2.5, respectively. Unexpectedly, during continuous fermentation with suspended cells, at a dilution rate of 0.01h(-1), steady-state was not achieved and regular oscillations occurred in all measured variables, i.e. concentrations of glycerol, products and the number of cells stained with the fluorescent dyes carboxy fluorescein diacetate and propidium iodide. A possible explanation for oscillatory/steady-state behavior of suspended/surface-attached cells, respectively, may be specific butanol toxicity (toxicity per cell), which was higher/lower in respective cases, and which might be caused by lower/higher cell numbers respectively in both systems.
- MeSH
- Bioreactors MeSH
- Biotechnology methods MeSH
- Clostridium cytology metabolism ultrastructure MeSH
- Fermentation MeSH
- Cells, Immobilized cytology metabolism ultrastructure MeSH
- Zea mays chemistry MeSH
- 1-Butanol metabolism MeSH
- Waste Products analysis MeSH
- Batch Cell Culture Techniques MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Continuous tablet manufacturing is a competitive option to replace the traditional batch manufacturing approach. The aim of this study was to evaluate technology transfer from batch-based direct compression of a commercial tablet formulation to continuous direct compression without changes to the composition of the formulation. Some powder studies were conducted with the raw materials and multi-tip punches were utilized in the tableting studies. To lower the high level of tablet weight variability that was evident during preliminary tests, a process parameter optimization was performed using an experimental design with different rpm values of force feeder and mixer impeller. By selecting the most appropriate settings of these parameters for the studied product, the weights of the tablets could be controlled adequately to meet the specification criteria. The functionality of the best-performing parameter settings was investigated with a three-hour-long tableting run. The tablets were evaluated with the same quality criteria as the commercial batch-produced tablets, and they passed all the tests performed in this study. Despite the challenging material properties according to the flowability tests, production of tablets with the desired quality was achieved using the original composition with continuous direct compression.
- MeSH
- Bisoprolol * MeSH
- Technology, Pharmaceutical * MeSH
- Powders MeSH
- Drug Compounding MeSH
- Tablets MeSH
- Pressure MeSH
- Publication type
- Journal Article MeSH
The transfer from batch-based to continuous tablet manufacturing increases the quality and efficiency of processes. Nonetheless, as in the development of a batch process, the continuous process design requires optimization studies to ensure a robust process. In this study, processing of a commercially batch-manufactured tablet product was tested with two continuous direct compression lines while keeping the original formulation composition and tablet quality requirements. Tableting runs were conducted with different values of process parameters. Changes in parameter settings were found to cause differences in tablet properties. Most of these quality properties could be controlled and maintained within the set limits effortlessly already at this stage of studies. However, the API content and content uniformity seemed to require more investigation. The observed content uniformity challenges were traced to individual tablets with a high amount of API. This was suspected to be caused by API micro-agglomerates since tablet weight variability did not explain the issue. This could be solved by adding a mill between two blenders in the process line. Overall, this case study produced promising results with both tested manufacturing lines since many tablet properties complied with the test result limits without optimization of process parameter settings.
Uvádíme recentní literární data o variabilitě výsledků laboratorních měření, způsobené změnami šarží reagencií, reagenčních systémů a kalibrátorů (lot-to-lot variation). Tato variabilita může být u některých analytů a metod měření velmi významná a je například popsána její velikost, přesahující 10%. Důsledky pro diagnostiku a pro hodnocení analytické kvality jsou významné. V případě glukometrů je variabilita mezi šaržemi reagencií aplikována do příslušné normy kvality ISO 15197, v ostatních případech však nebylo dosud její hodnocení a aplikace obvyklé. V sdělení uvádíme současné možnosti vyhodnocování těchto variací v hodnoceních různých šarží reagencií a kalibrátorů a v některých mezilaboratorních pokusech (Empower). Vyhodnocování variabilit mezi šaržemi by mělo být regulérní součástí procesů verifikace laboratorních metod a součástí verifikačních protokolů při akreditacích.
We deals with recently published data on the lot-to-lot variation in laboratory measurements by some important analytes. This variability can reach in some cases more than 10%. We discuss possible significant impacts for diagnostic processes and also for external quality assessment. Lot-to-lot variability in the diagnostic strips of glucose POCT and self-monitoring measurement systems are applied as integral part of ISO 15197 standard. We introduce ways and possibilities for establishment and assessment of these variations. Quantification and documentation of lot-to-lot variation is necessary tool for verification of measurement methods in clinical laboratories.
Wide ranges of growth yields on sulfur (from 2.4 x 10(10) to 8.1 x 10(11) cells g(-1)) and maximum sulfur oxidation rates (from 0.068 to 1.30 mmol liter(-1) h(-1)) of an Acidithiobacillus ferrooxidans strain (CCM 4253) were observed in 73 batch cultures. No significant correlation between the constants was observed. Changes of the Michaelis constant for sulfur (from 0.46 to 15.5 mM) in resting cells were also noted.
Severe corticosteroid-refractory graft-versus-host-disease (GVHD) is a major non-relapse cause of mortality and morbidity after an allogeneic hematopoietic stem cell transplantation (allo-HSCT). One of the most promising treatment options is using advanced therapy medicinal products based on mesenchymal stem cells (MSCs) immunomodulation ability. The protocols of MSC application differ in many parameters including a source of MSC, a dose, a number of doses or way of preparation of the medicinal product. The process is limited by the need for laborious and expensive manufacturing processes fraught with batch-to-batch variability. In our study, we compared the immunomodulatory effects of different MSC batches versus pooled MSC, specifically the influence on lymphocyte proliferation, the metabolic activity, and the expression of activation markers on T cells. Our goal was to determine whether the effect depends on donor-to-donor heterogeneity and if pooling of MSCs could increase their immunomodulatory ability. All tested batches showed an immunomodulatory effect, with no significant differences between the groups. Our study suggests that immunosuppressive potential is comparable in single batches and pooled products, and the use of products got from individual donors is suitable to treat corticosteroid-refractory GVHD.
- MeSH
- Lymphocyte Activation MeSH
- Tissue Donors MeSH
- Immunomodulation * MeSH
- Coculture Techniques MeSH
- Cells, Cultured MeSH
- Humans MeSH
- Mesenchymal Stem Cells cytology immunology MeSH
- Graft vs Host Disease etiology immunology therapy MeSH
- Cell Proliferation MeSH
- Cell Separation MeSH
- T-Lymphocytes cytology immunology MeSH
- Hematopoietic Stem Cell Transplantation adverse effects MeSH
- Mesenchymal Stem Cell Transplantation MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Comparative Study MeSH
A European round robin test according to ISO 5725-2 was conceptually prepared, realised, and evaluated. The aim was to determine the inter-laboratory variability of the overall process for the ecotoxicological characterization of construction products in eluates and bioassays. To this end, two construction products BAM-G1 (granulate) and HSR-2 (roof sealing sheet), both made of EPDM polymers (rubber), were selected. The granular construction product was eluted in a one stage batch test, the planar product in the Dynamic Surface Leaching test (DSLT). A total of 17 laboratories from 5 countries participated in the round robin test: Germany (12), Austria (2), Belgium (1), Czech Republic (1) and France (1). A test battery of four standardised ecotoxicity tests with algae, daphnia, luminescent bacteria and zebrafish eggs was used. As toxicity measures, EC50 and LID values were calculated. All tests, except the fish egg test, were basically able to demonstrate toxic effects and the level of toxicity. The reproducibility of test results depended on the test specimens and the test organisms. Generally, the variability of the EC50 or LID values increased with the overall level of toxicity. For the very toxic BAM-G1 eluate a relative high variability of CV = 73%-110% was observed for EC50 in all biotests, while for the less toxic HSR-2 eluate the reproducibility of EC50 varied with sensitivity: it was very good (CV = 9.3%) for the daphnia test with the lowest sensitivity, followed by the algae test (CV = 36.4%). The luminescent bacteria test, being the most sensitive bioassay for HSR-2 Eluate, showed the highest variability (CV = 74.8%). When considering the complex overall process the reproducibility of bioassays with eluates from construction products was acceptable.
- MeSH
- Bacteria drug effects MeSH
- Biological Assay methods standards MeSH
- Water Pollutants, Chemical analysis toxicity MeSH
- Zebrafish MeSH
- Daphnia drug effects MeSH
- Ecotoxicology methods standards MeSH
- Elastomers toxicity MeSH
- Ethylenes toxicity MeSH
- Rubber toxicity MeSH
- Stramenopiles drug effects MeSH
- Observer Variation MeSH
- Reproducibility of Results MeSH
- Toxicity Tests methods standards MeSH
- Eggs MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
OBJECTIVE: Radiographic assessment of sacroiliac joints (SIJs) according to the modified New York (mNY) criteria is key in the classification of axial spondyloarthritis but has moderate interreader agreement. We aimed to investigate the improvements of the reliability in scoring SIJ radiographs after applying an online real-time iterative calibration (RETIC) module, in addition to a slideshow and video alone. METHODS: Nineteen readers, randomized to 2 groups (A or B), completed 3 calibration steps: (1) review of manuscripts, (2) review of slideshow and video with group A completing RETIC, and (3) re-review of slideshow and video with group B completing RETIC. The RETIC module gave instant feedback on readers' gradings and continued until predefined reliability ([Formula: see text]) targets for mNY positivity/negativity were met. Each step was followed by scoring different batches of 25 radiographs (exercises I to III). Agreement ([Formula: see text]) with an expert radiologist was assessed for mNY positivity/negativity and individual lesions. Improvements by training strategies were tested by linear mixed models. RESULTS: In exercises I, II, and III, mNY [Formula: see text] were 0.61, 0.76, and 0.84, respectively, in group A; and 0.70, 0.68, and 0.86, respectively, in group B (ie, increasing, mainly after RETIC completion). Improvements were observed for grading both mNY positivity/negativity and individual pathologies, both in experienced and, particularly, inexperienced readers. Completion of the RETIC module in addition to the slideshow and video caused a significant [Formula: see text] increase of 0.17 (95% CI 0.07-0.27; P = 0.002) for mNY-positive and mNY-negative grading, whereas completion of the slideshow and video alone did not ([Formula: see text] = 0.00, 95% CI -0.10 to 0.10; P = 0.99). CONCLUSION: Agreement on scoring radiographs according to the mNY criteria significantly improved when adding an online RETIC module, but not by slideshow and video alone.
- MeSH
- Axial Spondyloarthritis * diagnostic imaging MeSH
- Humans MeSH
- Observer Variation * MeSH
- Radiography * methods MeSH
- Reproducibility of Results MeSH
- Sacroiliac Joint * diagnostic imaging MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Randomized Controlled Trial MeSH
Příznaky z postižení zažívacího traktu bývají u nemocných s primárními imunodeficienciemi poměrně časté. U kombinovaných (T+B) deficiencí mohou být těžké chronické průjmy první klinickou manifestací postižení imunitního systému. Z protilátkových imunodeficiencí se gastrointestinální symptomatologie vyskytuje především při běžné variabilní imunodeficienci (CVID). U části nemocných s CVID se v poměrně mladém věku objevuje atrofická gastritida, s ní zřejmě souvisí i zvýšený výskyt karcinomu žaludku. Při chronických průjmech pacientů s CVID je třeba myslet především na infekci Giardia lamblia. Chronické nebo rekurentní průjmy se mohou objevovat i u dalších protilátkových imunodeficiencí. U většiny chorob z poruchy tvorby protilátek se častěji než v běžné populaci objevují nespecifické střevní záněty, někdy s atypickými histologickými nálezy. Časté postižení jater u agamaglobulinemiků zřejmě souvisí s imunoglobulinovou léčbou. Část nemocných byla dříve infikována imunoglobulinovými deriváty kontaminovanými virem hepatitidy C (HCV), abnormální jaterní testy se však objevují i u řady pacientů, u nichž není předchozí infekce HCV prokazatelná.
Gastrointestinal symptoms are frequent in primary immunodeficiency diseases. Severe chronic diarrhoea may be a first symptom of combined (T+B) immunodeficiency. In humoral immunodeficiencies, gastrointestinal symptomatology is most frequently met in common variable immunodeficiency (CVID). These patients suffer from atrophic gastritis with onset in a young age, gastritis probably predisposes to a gastric cancer which is also frequent in CVID patients. In a case of chronic diarrhoea infection of Giardia lamblia should be suspected. Chronic or recurrent diarrhoeas can also be observed in other humoral immunodeficiencies. Non-specific inflammatory bowel diseases seem to be more frequent in patients with humoral immunodeficiencies than in general population, unusual histopathologic findings can be observed in some cases. Frequent hepatobiliary diseases in agammaglobulinemic patients are frequently associated with immunoglobulin replacement treatment. Some patients were infected by the hepatitis C virus by contaminated batches of intravenous immunoglobulins, but abnormal liver function tests were also observed in many patients without any laboratory signs of hepatitis-C virus infection.
- MeSH
- Common Variable Immunodeficiency complications MeSH
- Research Support as Topic MeSH
- Gastritis, Atrophic etiology microbiology MeSH
- Gastrointestinal Diseases etiology MeSH
- Liver Diseases etiology MeSH
- Intestinal Diseases etiology MeSH
- Signs and Symptoms MeSH
- Diarrhea history etiology MeSH
- Publication type
- Review MeSH
