Assessment of immunogenicity of romiplostim in clinical studies with ITP subjects

Romiplostim is an Fc-peptide fusion protein that activates intracellular transcriptional pathways via the thrombopoietin (TPO) receptor leading to increased platelet production. Romiplostim has been engineered to have no amino acid sequence homology to endogenous TPO. Recombinant protein therapeutics can be at a risk of development of an antibody response that can impact efficacy and safety. Hence, a strategy to detect potential antibody formation to the drug and to related endogenous molecules can be useful. The immunogenicity assessment strategy involved both the detection and characterization of binding and neutralizing antibodies. The method for detection was based on a surface plasmon resonance biosensor platform using the Biacore 3000. Samples that tested positive for binding antibodies in the Biacore immunoassay were then tested in a neutralization assay. Serum samples from 225 subjects with immune thrombocytopenic purpura (ITP) dosed with romiplostim and 45 ITP subjects dosed with placebo were tested for romiplostim and TPO antibodies. Prior to romiplostim treatment, 17 subjects (7%) tested romiplostim antibody positive and 12 subjects (5%) tested TPO antibody positive for pre-existing binding antibodies. After romiplostim exposure, 11% of the subjects exhibited binding antibodies against romiplostim and 5% of the subjects with ITP showed binding antibodies against TPO. The antibodies against romiplostim did not cross-react with TPO and vice versa. No cases of anti-TPO neutralizing antibodies were detected in romiplostim-treated subjects. The incidence of anti-romiplostim neutralizing antibodies to romiplostim was 0.4% (one subject); this subject tested negative at the time of follow-up 4 months later. No impact on platelet profiles were apparent in subjects that had antibodies to romiplostim to date. In summary, administration of romiplostim in ITP subjects resulted in the development of a binding antibody response against romiplostim and TPO ligand. One subject developed a neutralizing antibody response to romiplostim that impacted the platelet counts of this subject. No neutralizing antibodies to endogenous TPO were observed

Consideration of the bioavailability of metal/metalloid species in freshwaters: experiences regarding the implementation of biotic ligand model-based approaches in risk assessment frameworks

After the scientific development of Biotic Ligand Models (BLMs) in recent decades these models are now considered suitable for implementation in regulatory risk assessment of metals in freshwater bodies. The approach has been developed over several years and has been described in many peer-reviewed publications. The original complex BLMs have been applied in prospective risk assessment reports for metals and metal compounds and are also recommended as suitable concepts for the evaluation of monitoring data in the context of the European Water Framework Directive. Currently, several user-friendly BLM-based bioavailability software tools are available for assessing the aquatic toxicity of a limited number of metals (mainly copper, nickel, and zinc). These tools need only a basic set of water parameters as input (e.g., pH, hardness, dissolved organic matter and dissolved metal concentration). Such tools seem appropriate to foster the implementation in routine water quality assessments. This work aims to review the existing bioavailability-based regulatory approaches and the application of available BLM-based bioavailability tools for this purpose. Advantages and possible drawbacks of these tools (e.g., feasibility, boundaries of validity) are discussed, and recommendations for further implementation are given

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Investigating the conditions for functioning of the accredited quality management system in a research laboratory - research concept

Artykuł opisuje koncepcję badania uwarunkowań funkcjonowania akredytowanego systemu zarządzania jakością w akredytowanym laboratorium badawczym. W Polsce jednostką udzielającą akredytacji jest Polskie Centrum Akredytacji. Do tej pory analizowane były m.in. procesy badawcze i proces akredytacji. Nie prowadzono badań dotyczących funkcjonowania akredytowanego systemu zarządzania jakością w laboratoriach badawczych. Niniejszy artykuł przedstawia sposób wyboru grupy badawczej oraz etapy prowadzenia badań. Praca w dalszej części zmierza do zbadania uwarunkowań funkcjonowania akredytowanego systemu zarządzania jakością oraz określenia obszarów systemu zarządzania jakością, które stwarzają laboratoriom najwięcej problemów.The work describes the concept of investigation conditions of accreditation quality management system in a research laboratory. In Poland, the institution that granting accreditation is Polish Centre for Accreditation. Until now, theresearch processes and the accreditation process have been analyzed, but there were no studies on the functioning of the quality management system in accredited testing laboratories. This article shows how will be selected the research group and the stages taking under research. The work aims to investigate the conditions functioning of an accredited quality management system and identify areas of quality management system, which create laboratories most problems

Badanie wpływu struktury organizacyjnej na funkcjonowanie akredytowanego laboratorium badawczego

The quality management systems compliant with the PN-EN ISO/IEC 17025:2005 standard are widely described in terms of the research methods. However, the construction and functioning of the management system are discussed on a much smaller scale. The Authors of this publication tried to assess selected results from the survey conducted among 1,213 accredited testing laboratories functioning in Poland. The Authors focused on analysing the survey results describing the influence of the organizational structure of the institution in which the laboratory was located on the functioning of an accredited management system in a testing laboratory.ystemy zarządzania jakością wg normy PN-EN ISO/IEC 17025:2005 zostały szeroko opisane w kontekście metod badawczych. Natomiast budowa i funkcjonowanie systemu zarządzania zostały opisane w znacznie mniejszej skali. Autorzy publikacji podjęli próbę oceny wybranych wyników przeprowadzonego badania ankietowego na próbie 1213 akredytowanych laboratoriów badawczych funkcjonujących na terenie Polski. Autorzy skupili się na analizie wyników ankiety opisującej wpływ struktury organizacyjnej jednostki, w której jest umiejscowione laboratorium, na funkcjonowanie akredytowanego systemu zarządzania w laboratorium badawczym

Modern diagnostic devices aiding the industrial oven condition monitoring

O żywotności i osiąganej zdolności produkcyjnej pieców przemysłowych decyduje ich stan techniczno-technologiczny. Mając powyższe na względzie Instytut Chemicznej Przeróbki Węgla od wielu lat prowadzi specjalistyczne oceny pieców, w tym głównie pieców koksowniczych. Dla usprawnienia i ujednolicenia tych ocen, w ramach realizowanego projektu badawczego „Inteligentna Koksownia spełniająca wymagania najlepszej dostępnej techniki”, wypracowano w Instytucie „Zintegrowany komputerowy system monitorowania stanu technicznego baterii koksowniczych”. Choć system ten bazuje głównie na wynikach wizualnych przeglądów stanu ceramiki i parametrach technologicznych odnotowywanych on-line w systemie bieżącej kontroli eksploatacji baterii, to jednak coraz częściej jego uzupełnieniem stają się ostatnio specjalistyczne analizy obrazów termowizyjnych i endoskopowych.The condition of and technology used in the industrial oven determine its life and production capacity. With that in mind, for many years the Institute for Chemical Processing of Coal in Zabrze (Instytut Chemicznej Przeróbki Węgla) has been carrying out specialised evaluations of industrial ovens, focusing predominantly on coke ovens. To improve and standardise the evaluations, an “Integrated computer system for coke battery condition monitoring” was produced as part of an ongoing research project “An Intelligent Coke Oven compliant with the requirements of the best modern technologies”.The system processes predominantly visual surveys of the condition of ceramic materials as well as technical parameters submitted online to a continuous battery monitoring system. However, it has been more and more frequently complemented by specialised analyses of thermal imaging data and endoscopic inspections

Evaluation of the functioning accredited quality management system in the research laboratory – research survey results

Systemy zarządzania jakością wg normy ISO 9001:2009 zostały szeroko opisane i przebadane. Akredytowane systemy zarządzania w laboratoriach badawczych wg ISO/IEC 17025:2005 opisywanie były głównie pod kątem tworzenia i wdrażania systemu, a także pod kątem analitycznym. Mało miejsca poświęcono badaniom funkcjonowania systemu zarządzania w akredytowanych laboratoriach badawczych. W niniejszej pracy zostały przedstawione wybrane wyniki badań ankietowych przeprowadzonych na grupie 1213 akredytowanych laboratoriów badawczych.Quality management systems according to ISO 9001: 2009 has been thoroughly described and examined. Accredited management systems in research laboratories according to ISO / IEC 17025: 2005 were describing mainly for the creation and implementation of the system, as well as for analytical point of view. A low number of studies concerned to examine the functioning of the management in accredited laboratories. In this work are presented selected results of a survey conducted on a group of 1,213 accredited laboratories