On the reliability of multistate systems with imprecise probabilities

Розглядається обчислення надійності в складних системах за наявності випадкового набору оцінок працездатності елементів. Виявлено, що підхід Демпстер-Шефера є відповідним математичним інструментом, який відповідає поставленим задачам. Для випадку, коли взаємозалежності елементів невідомі, наведено також оцінки ефективності системи переконань і правдоподібність функції.Рассматривается вычисления надежности в сложных системах при наличии случайного набора оце- нок работоспособности элементов. Выявлено, что подход Демпстер-Шефера является соответствующим математическим инструментом, который соответствует поставленным задачам. Для случая, когда взаимозависимости элементов неизвестны, приведены также оценки эффективности системы убеждений и правдоподобность функции.We consider the computation of multistate systems reliabilities in the presence of random set estimations for the elements' working abilities. It turns out that the Dempster-Shafer approach is a suitable mathematical tool. For the case that the interdependence of the elements is unknown, bounds for the system's performance belief and plausibility functions are given as well

The SEURAT-1 Approach towards Animal Free Human Safety Assessment

SEURAT-1 is a European public-private research consortium that is working towards animal-free testing of chemical compounds and the highest level of consumer protection. A research strategy was formulated based on the guiding principle to adopt a toxicological mode-of-action framework to describe how any substance may adversely affect human health. The proof of the initiative will be in demonstrating the applicability of the concepts on which SEURAT-1 is built on three levels: (i) Theoretical prototypes for adverse outcome pathways are formulated based on knowledge already available in the scientific literature on investigating the toxicological modes-of-action leading to adverse outcomes (addressing mainly liver toxicity); (ii) adverse outcome pathway descriptions are used as a guide for the formulation of case studies to further elucidate the theoretical model and to develop integrated testing strategies for the prediction of certain toxicological effects (i.e., those related to the adverse outcome pathway descriptions); (iii) further case studies target the application of knowledge gained within SEURAT-1 in the context of safety assessment. The ultimate goal would be to perform ab initio predictions based on a complete understanding of toxicological mechanisms. In the near-term, it is more realistic that data from innovative testing methods will support read-across arguments. Both scenarios are addressed with case studies for improved safety assessment. A conceptual framework for a rational integrated assessment strategy emerged from designing the case studies and is discussed in the context of international developments focusing on alternative approaches for evaluating chemicals using the new 21st century tools for toxicity testing

Transient parkinsonism in isolated extrapontine myelinolysis

Extrapontine myelinolysis (EPM) is a rare cause of parkinsonism. In this case report, we describe a 63-year-old woman with parkinsonism due to EPM after correction of hyponatremia. During a 4-year follow-up, both the clinical features of parkinsonism and the changes on magnetic resonance imaging resolved. Parkinsonism due to EPM should be recognized as it has a good prognosis

emerging perspectives for flood risk assessment and management

Flood estimation and flood management have traditionally been the domain of hydrologists, water resources engineers and statisticians, and disciplinary approaches abound. Dominant views have been shaped; one example is the catchment perspective: floods are formed and influenced by the interaction of local, catchment-specific characteristics, such as meteorology, topography and geology. These traditional views have been beneficial, but they have a narrow framing. In this paper we contrast traditional views with broader perspectives that are emerging from an improved understanding of the climatic context of floods. We come to the following conclusions: (1) extending the traditional system boundaries (local catchment, recent decades, hydrological/hydraulic processes) opens up exciting possibilities for better understanding and improved tools for flood risk assessment and management. (2) Statistical approaches in flood estimation need to be complemented by the search for the causal mechanisms and dominant processes in the atmosphere, catchment and river system that leave their fingerprints on flood characteristics. (3) Natural climate variability leads to time-varying flood characteristics, and this variation may be partially quantifiable and predictable, with the perspective of dynamic, climate-informed flood risk management. (4) Efforts are needed to fully account for factors that contribute to changes in all three risk components (hazard, exposure, vulnerability) and to better understand the interactions between society and floods. (5) Given the global scale and societal importance, we call for the organization of an international multidisciplinary collaboration and data-sharing initiative to further understand the links between climate and flooding and to advance flood research

Floods and climate: emerging perspectives for flood risk assessment and management

Flood estimation and flood management have traditionally been the domain of hydrologists, water resources engineers and statisticians, and disciplinary approaches abound. Dominant views have been shaped; one example is the catchment perspective: floods are formed and influenced by the interaction of local, catchment-specific characteristics, such as meteorology, topography and geology. These traditional views have been beneficial, but they have a narrow framing. In this paper we contrast traditional views with broader perspectives that are emerging from an improved understanding of the climatic context of floods. We come to the following conclusions: (1) extending the traditional system boundaries (local catchment, recent decades, hydrological/hydraulic processes) opens up exciting possibilities for better understanding and improved tools for flood risk assessment and management. (2) Statistical approaches in flood estimation need to be complemented by the search for the causal mechanisms and dominant processes in the atmosphere, catchment and river system that leave their fingerprints on flood characteristics. (3) Natural climate variability leads to time-varying flood characteristics, and this variation may be partially quantifiable and predictable, with the perspective of dynamic, climate-informed flood risk management. (4) Efforts are needed to fully account for factors that contribute to changes in all three risk components (hazard, exposure, vulnerability) and to better understand the interactions between society and floods. (5) Given the global scale and societal importance, we call for the organization of an international multidisciplinary collaboration and data-sharing initiative to further understand the links between climate and flooding and to advance flood research

Thresholds of Toxicological Concern for Cosmetics-Related Substances: New Database, Thresholds, and Enrichment of Chemical Space

A new dataset of cosmetics-related chemicals for the Threshold of Toxicological Concern (TTC) approach has been compiled, comprising 552 chemicals with 219, 40, and 293 chemicals in Cramer Classes I, II, and III, respectively. Data were integrated and curated to create a database of No-/Lowest-Observed-Adverse-Effect Level (NOAEL/LOAEL) values, from which the final COSMOS TTC dataset was developed. Criteria for study inclusion and NOAEL decisions were defined, and rigorous quality control was performed for study details and assignment of Cramer classes. From the final COSMOS TTC dataset, human exposure thresholds of 42 and 7.9 μg/kg-bw/day were derived for Cramer Classes I and III, respectively. The size of Cramer Class II was insufficient for derivation of a TTC value. The COSMOS TTC dataset was then federated with the dataset of Munro and colleagues, previously published in 1996, after updating the latter using the quality control processes for this project. This federated dataset expands the chemical space and provides more robust thresholds. The 966 substances in the federated database comprise 245, 49 and 672 chemicals in Cramer Classes I, II and III, respectively. The corresponding TTC values of 46, 6.2 and 2.3 μg/kg-bw/day are broadly similar to those of the original Munro dataset

Diagnosis of inflammatory demyelination in biopsy specimens: a practical approach

Multiple sclerosis is the most frequent demyelinating disease in adults. It is characterized by demyelination, inflammation, gliosis and a variable loss of axons. Clinically and histologically, it shares features with other demyelinating and/or inflammatory CNS diseases. Diagnosis of an inflammatory demyelinating disease can be challenging, especially in small biopsy specimens. Here, we summarize the histological hallmarks and most important neuropathological differential diagnoses of early MS, and provide practical guidelines for the diagnosis of inflammatory demyelinating diseases

The life and scientific work of William R. Evitt (1923-2009)

Occasionally (and fortunately), circumstances and timing combine to allow an individual, almost singlehandedly, to generate a paradigm shift in his or her chosen field of inquiry. William R. (‘Bill’) Evitt (1923-2009) was such a person. During his career as a palaeontologist, Bill Evitt made lasting and profound contributions to the study of both dinoflagellates and trilobites. He had a distinguished, long and varied career, researching first trilobites and techniques in palaeontology before moving on to marine palynomorphs. Bill is undoubtedly best known for his work on dinoflagellates, especially their resting cysts. He worked at three major US universities and spent a highly significant period in the oil industry. Bill's early profound interest in the natural sciences was actively encouraged both by his parents and at school. His alma mater was Johns Hopkins University where, commencing in 1940, he studied chemistry and geology as an undergraduate. He quickly developed a strong vocation in the earth sciences, and became fascinated by the fossiliferous Lower Palaeozoic strata of the northwestern United States. Bill commenced a PhD project on silicified Middle Ordovician trilobites from Virginia in 1943. His doctoral research was interrupted by military service during World War II; Bill served as an aerial photograph interpreter in China in 1944 and 1945, and received the Bronze Star for his excellent work. Upon demobilisation from the US Army Air Force, he resumed work on his PhD and was given significant teaching duties at Johns Hopkins, which he thoroughly enjoyed. He accepted his first professional position, as an instructor in sedimentary geology, at the University of Rochester in late 1948. Here Bill supervised his first two graduate students, and shared a great cameraderie with a highly motivated student body which largely comprised World War II veterans. At Rochester, Bill continued his trilobite research, and was the editor of the Journal of Paleontology between 1953 and 1956. Seeking a new challenge, he joined the Carter Oil Company in Tulsa, Oklahoma, during 1956. This brought about an irrevocable realignment of his research interests from trilobites to marine palynology. He undertook basic research on aquatic palynomorphs in a very well-resourced laboratory under the direction of one of his most influential mentors, William S. ‘Bill’ Hoffmeister. Bill Evitt visited the influential European palynologists Georges Deflandre and Alfred Eisenack during late 1959 and, while in Tulsa, first developed several groundbreaking hypotheses. He soon realised that the distinctive morphology of certain fossil dinoflagellates, notably the archaeopyle, meant that they represent the resting cyst stage of the life cycle. The archaeopyle clearly allows the excystment of the cell contents, and comprises one or more plate areas. Bill also concluded that spine-bearing palynomorphs, then called hystrichospheres, could be divided into two groups. The largely Palaeozoic spine-bearing palynomorphs are of uncertain biological affinity, and these were termed acritarchs. Moreover, he determined that unequivocal dinoflagellate cysts are all Mesozoic or younger, and that the fossil record of dinoflagellates is highly selective. Bill was always an academic at heart and he joined Stanford University in 1962, where he remained until retiring in 1988. Bill enjoyed getting back into teaching after his six years in industry. During his 26-year tenure at Stanford, Bill continued to revolutionise our understanding of dinoflagellate cysts. He produced many highly influential papers and two major textbooks. The highlights include defining the acritarchs and comprehensively documenting the archaeopyle, together with highly detailed work on the morphology of Nannoceratopsis and Palaeoperidinium pyrophorum using the scanning electron microscope. Bill supervised 11 graduate students while at Stanford University. He organised the Penrose Conference on Modern and Fossil Dinoflagellates in 1978, which was so successful that similar meetings have been held about every four years since that inaugural symposium. Bill also taught many short courses on dinoflagellate cysts aimed at the professional community. Unlike many eminent geologists, Bill actually retired from actively working in the earth sciences. His full retirement was in 1988; after this he worked on only a small number of dinoflagellate cyst projects, including an extensive paper on the genus Palaeoperidinium