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Prescription-event monitoring (PEM) is the current gold standard for determining the risk of rare drug side-effects and comparing the risk between agents; however, spontaneous or prompted reporting schemes have low case-detection rates and exposure may be difficult to estimate. A novel method is described that allows a comparative adverse event rate between two drugs to be estimated—based on patterns of cross-reactivity—requiring only a sample of cases and no direct knowledge of drug exposure rates. Agreement was compared between the novel method and historical estimates of risk using PEM for comparative risk of rocuronium versus vecuronium anaphylaxis. The novel method was applied to a sample of patients investigated by the Western Australian Anaesthetic Drug Reaction Clinic over a 21-year period. Relative population exposure was estimated from the number of patients with either rocuronium or vecuronium anaphylaxis subsequently shown to be reactive on skin testing to both agents. This was used to correct the total number of cases of hypersensitivity triggered by each agent. Measures of spread were by bootstrap sampling. Historical estimates were gathered by literature review. Additional comparisons of agreement between estimates made by the novel method and PEM were made using cross-reactivity data and PEM rates reported in the literature. There was agreement between estimates of comparative anaphylaxis risk between the novel method and PEM. Two-hundred and twenty-eight cases of anaphylaxis were observed, 89% caused by rocuronium. Patients reactive to both agents were more likely to be female, and had a higher acute mast cell tryptase level. Patients with a history of rocuronium anaphylaxis were more likely to be reactive to one agent only (69% vs. 33%, P < 0.01). It was estimated that rocuronium was prescribed 3.9 times more frequently than vecuronium. When the observed proportion of cases was corrected for exposure rate, the risk of rocuronium anaphylaxis was 2.2 times that of vecuronium (95% confidence interval 1.7 to 2.8). The median risk from historical estimates was 4.7 times, while the previous PEM estimate in Western Australian was 3.0 times. Using a subgroup of patients susceptible to the same side-effect of two drugs, the relative exposure rate and corrected comparative risk of an adverse effect can be estimated for a population. Using this technique, which requires assessment only of cases to estimate relative exposure rates, we have estimated that the risk of anaphylaxis from rocuronium to be 2.2 times that of vecuronium in Western Australia. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a highly heterogeneous cancer, and resistant to both conventional and targeted chemotherapy. Recently, nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to decrease the incidence and mortality of different types of cancers. Here, we investigated the cellular bioactivities of a series of triazolothiadiazine derivatives on HCC, which have been previously reported as potent analgesic/anti-inflammatory compounds. From the initially tested 32 triazolothiadiazine NSAID derivatives, 3 compounds were selected based on their IC50 values for further molecular assays on 9 different HCC cell lines. 7b, which was the most potent compound, induced G2/M phase cell cycle arrest and apoptosis in HCC cells. Cell death was due to oxidative stress-induced JNK protein activation, which involved the dynamic involvement of ASK1, MKK7, and c-Jun proteins. Moreover, 7b treated nude mice had a significantly decreased tumor volume and prolonged disease-free survival. 7b also inhibited the migration of HCC cells and enrichment of liver cancer stem cells (LCSCs) alone or in combination with sorafenib. With its ability to act on proliferation, stemness and the migration of HCC cells, 7b can be considered for the therapeutics of HCC, which has an increased incidence rate of ~ 3% annually. [ABSTRACT FROM AUTHOR]

The full-resolution next generation impactor (NGI) and three abbreviated impactor systems were used to obtain the apparent aerodynamic particle size distribution (APSD) and other quality measures for marketed dry powder inhalers (DPIs) using the compendial method and efficient data analysis (EDA). APSD for the active pharmaceutical ingredient (API) in Spiriva Handihaler, Foradil Aerolizer, and Relenza Diskhaler was obtained using a full-resolution NGI at 39, 60, and 90 L/min, respectively. Two reduced NGI (rNGI) configurations, the filter-only configuration (rNGI-f) and the modified-cup configuration (rNGI-mc), and the fast-screening impactor (FSI) with appropriate inserts to provide a 5-μm cut size were evaluated. The fine particle dose (FPD) obtained using the FSI for Spiriva was statistically similar to that obtained using the full NGI. However, the FPD for both Foradil and Relenza obtained using the FSI was significantly different from that obtained using the full NGI. Despite this, no significant differences were observed for the fine particle fraction (FPF) obtained using the FSI relative to that obtained from the full NGI for any of the DPIs. The use of abbreviated impactor systems appears promising with good agreement observed with the full-resolution NGI, except for small differences observed for the rNGI-mc configuration. These small differences may be product- and/or flow rate-specific, and further evaluation will be required to resolve these differences. [ABSTRACT FROM AUTHOR]

Focuses on the study involving the television program `Second Show' and its effect on Israeli children's perception of social reality. Background of the research; Method used for the study; Result and discussion.

The article presents an update of the case law relating to the Brussels Convention of 1968 on Jurisdiction and the Enforcement of Judgments in Civil and Commercial Matters. According to the article, the ruling in Sonntag v. Waidmann, confirmed that a claim for damages resulting from a criminal act, introduced in the course of criminal proceedings against the culpable person, constitutes a civil matter, except if the author of the damage is to be regarded as a public authority acting in the exercise of public powers. In Marinari v. Lloyds Bank and Zubaidi, the European Court of Justice emphasized that the term "place where the harmful event occurred" should not be interpreted as concerning the place where the victim claims to have suffered damage to certain assets.

Research findings in the last decade indicated that although situation comedies were most popular with children, most children did not fully understand the moral of stories or the messages conveyed. Psychologists expressed concern that an adequate comprehension of messages in this genre may require complex intellectual operations which young viewers were not capable of. A broadcast presenting deceitful behaviour in a situation comedy, tested among 314 9‐12 year old children in Israel, had no immediate effect on the perception of children vis‐à‐vis norms of behaviour in their surroundings. The degree of understanding increased with age as did the level of children's critical approach and moral judgement of deceitful behaviour in the broadcast. Young viewers regarded negative behaviour presented on the screen as wrong. Evaluations of such behaviours on TV were independent of children's perception regarding the norms of behaviour in their real life environment. The study revealed that even at the age of 9, Israeli children display a high degree of understanding of motives and effects presented in a situation comedy. Sympathy for TV characters was not based on the characters’ moral/immoral behaviour, but rather on their entertaining appearance and quality of acting. [ABSTRACT FROM PUBLISHER]

This paper deals with the philosophical questions which gave rise to the traditional realist theories of universals. The main thesis is that these same questions may also be interpreted as scientific-empirical questions. The study of these problems has begun only very recently and the relevance of the results for the traditional problem of intensional entities has only been remarked by few workers aware of the philosophical problem. The approach adopted here is that of regarding man as a perceptual system situated in an environment and showing certain capacities like perception of 'universals'. The possible ways of access to these entities is discussed on the basis of some recent empirical findings related to perception. One conclusion is that in order to answer the basic philosophical question of how properties, particulars and propositions are perceived may be answered within the domains of science, accepting only the usual presuppositions used in it. Basically, such an approach sees the root of the problem in the great complexity of information processing involved in the actual perception of properties, particulars and propositions. [ABSTRACT FROM AUTHOR]

Presents information on a study conducted to determine the natural coordinate system for phylogenetic trees using a correspondence with the set of perfect matchings in the complete graph. Overview of the use of phylogenetic methodology in the exploration of tree space; Details on perfect matching of phylogenetic trees; Details on the New Hampshire and Newick format of tree representation.