Stir bar sorptive extraction of diclofenac from liquid formulations: A proof of concept study

A new stir bar sorptive extraction (SBSE) technique coupled with HPLC-UV method for quantification of diclofenac in pharmaceutical formulations has been developed and validated as a proof of concept study. Commercially available polydimethylsiloxane stir bars (Twister (TM)) were used for method development and SBSE extraction (pH, phase ratio, stirring speed, temperature, ionic strength and time) and liquid desorption (solvents, desorption method, stirring time etc) procedures were optimised. The method was validated as per ICH guidelines and was successfully applied for the estimation of diclofenac from three liquid formulations viz. Voltarol (R) Optha single dose eye drops, Voltarol (R) Ophtha multidose eye drops and Voltarol (R) ampoules. The developed method was found to be linear (r=0.9999) over 100-2000 ng/ml concentration range with acceptable accuracy and precision (tested over three QC concentrations). The SBSE extraction recovery of the diclofenac was found to be 70% and the LOD and LOQ of the validated method were found to be 16.06 and 48.68 ng/ml, respectively. Furthermore, a forced degradation study of a diclofenac formulation leading to the formation of structurally similar cyclic impurity (indolinone) was carried out. The developed extraction method showed comparable results to that of the reference method, i.e. method was capable of selectively extracting the indolinone and diclofenac from the liquid matrix. Data on inter and intra stir bar accuracy and precision further confirmed robustness of the method, supporting the multiple re-use of the stir bars. (C) 2010 Elsevier B.V. All rights reserved.

Development of an egg hatch assay for the diagnosis of triclabendazole resistance in Fasciola hepatica: proof of concept.

The aim of this study was to develop an Egg Hatch Assay (EHA) test for the detection of triclabendazole (TCBZ) resistance in Fasciola hepatica. A number of fluke isolates were used, of differing sensitivity to TCBZ. Eggs were exposed to solutions of triclabendazole sulphoxide (TCBZ.SO) for 14 days, then triggered to hatch. Egg development was divided into 6 distinct and easily identifiable stages: dead, empty, unembryonated, cell division, eye spot and hatched. The number of eggs reaching those stages was recorded. Initially, the discriminating dose (1% hatch) was determined for the Cullompton isolate, used as TCBZ-susceptible (TCBZ-S) standard. Once this concentration had been resolved, the response of different isolates to this concentration was examined. The hatch rate of the Fairhurst isolate was not significantly different from that of the Cullompton isolate, confirming its TCBZ-S status. The Patagonia isolate has not been exposed to TCBZ in the field and should be TCBZ-S: the results of the EHA supported this. The egg hatch response of the Oberon and Dutch isolates differed significantly from that of the Cullompton isolate; the former isolates are regarded as TCBZ-resistant (TCBZ-R) and the results confirmed this. Another isolate, the Leon isolate, was originally described as being TCBZ-R, but has since been shown to be TCBZ-S. There was no difference in its response to TCBZ.SO in the EHA from the Cullompton (and Fairhurst and Patagonia) isolate(s), further indicating its TCBZ-S status. The impact of TCBZ.SO treatment on the component stages of egg development was determined and revealed differences between the isolates. In conclusion, the results of the study have shown that it is possible to discriminate between TCBZ-S and TCBZ-R isolates of F. hepatica on the basis of the response of their eggs to an EHA and the test could be used to evaluate the TCBZ sensitivity of unknown field isolates

Polybius’ ‘previous landslide’: Proof that Hannibal’s invasion route crossed the col de la traversette

Both Polybius and Livy described a landslide/landslip that blocked the Punic Army’s exfiltration from a high col on the water divide in the Western Alps. The landslide, more aptly termed rockfall, has been a source of contention amongst classicists for centuries despite the fact that only two cols—Clapier and Traversette—exhibit rockfall debris on the lee side of the Alps. While the Clapier rockfall is too small and too young to have provided blockage, the Traversette debris is nearly as Polybius described it when he retraced the invasion route some 60 years after the event. His ‘two-tier’ description of the deposit, a doublet of younger and older rock rubble, including measurements of width and volume are close to modern measurements and prove that he knew, in advance, the route Hannibal had followed. It would take a practiced eye to correctly identify the stratigraphic complexity inherent in the Traversette Rockfall. Here we present weathering ratios, soil stratigraphic, mineral, chemical and microbiological evidence in support of Polybius’ observations as a considerable background database for future geoarchaeological exploration.

On the Ontological Quality and Logical Quality of Conceptual-Modeling Grammars: The Need for a Dual Perspective

A core activity in information systems development involves building a conceptual model of the domain that an information system is intended to support. Such models are created using a conceptual-modeling (CM) grammar. Just as high-quality conceptual models facilitate high-quality systems development, high-quality CM grammars facilitate high-quality conceptual modeling. This paper provides a new perspective on ways to improve the quality of the semantics of CM grammars. For many years, the leading approach to this topic has relied on ontological theory. We show, however, that the ontological approach captures only half the story. It needs to be coupled with a logical approach. We explain how the ontological quality and logical quality of CM grammars interrelate. Furthermore, we outline three contributions that a logical approach can make to evaluating the quality of CM grammars: a means of seeing some familiar conceptual-modeling problems in simpler ways; the illumination of new problems; and the ability to prove the benefit of modifying existing CM grammars in particular ways. We demonstrate these benefits in the context of the Entity-Relationship grammar. More generally, our paper opens up a new area of research with many opportunities for future research and practice.

The sound of a breaking string: critical environmental law and ontological vulnerability

This is a thought-provoking contribution on the space of ontological vulnerability as the awareness of being existentially exposed. This space, conceptualised as a space of ‘the middle’ (as opposed, emphatically, to ‘the centre’) offers an opportunity to think away from the sterile debate on eco/anthropocentricity and from such limiting hierarchies as animal/human, human/environmental, natural/artificial. This new, vulnerable position of the middle allows the reconfiguration of ecological processes, and more specifically the position of environmental law in relation to them. Environmental law now finds itself amidst a new, moving, ‘open ecology’ of social, biological and ecological processes. This is a new, radical conceptualisation of what the author has called ‘critical environmental law,’ based upon an epistemology of observation and an ontology of being part of this open ecology. Environmental law, in this light, is simultaneously reformulated as an invitation to disciplinary and ontological openness and yet a call to remain immanent within existing legal structures. This finds expression in four critical environmental positions that set the stage for the further elaboration of a critical environmental law.

Natural deduction system in paraconsistent setting: proof search for PCont

This paper continues a systematic approach to build natural deduction calculi and corresponding proof procedures for non-classical logics. Our attention is now paid to the framework of paraconsistent logics. These logics are used, in particular, for reasoning about systems where paradoxes do not lead to the `deductive explosion', i.e., where formulae of the type `A follows from false', for any A, are not valid. We formulate the natural deduction system for the logic PCont, explain its main concepts, define a proof searching technique and illustrate it by examples. The presentation is accompanied by demonstrating the correctness of these developments.

Digital evidence as a means of proof before the International Court of Justice

This article discusses the use of digital evidence as a means of proof before the International Court of Justice (ICJ). The absence of specific Court rules and procedures for digital evidence (with the exception of Practice Direction IX bis) is not necessarily an obstacle to its production and evaluation before the ICJ, as the general evidentiary rules can also be applied to digital evidence. The article first looks at the rules on the production of documentary evidence and then examines the specific issues related to audiovisual evidence. Finally, it examines the admissibility of digital evidence unlawfully obtained by a litigant through unilateral transborder access to data. The article concludes that, even if specific regulation may be needed as to the specific way in which authenticity and accuracy of digital evidence are to be established, the particular facts of the case and the grounds of challenge can vary widely, and it is doubtful that any regulation could be sufficiently flexible to deal with this in advance.

Proof of Concept of the Electrochemical Sensing of 3-Iodothyronamine (T1AM) and Thyronamine (T0AM)

Recent studies have shown that, besides the well-recognized T3 and T4 hormones, there are other relevant thyroid hormones circulating in the human body. In particular, this is the case for 3-iodothyronamine (T1AM) and thyronamine (T0AM). One of the reasons for the lack of studies showing their precise importance is the absence of analytical methodologies available. Herein, for the first time, T1AM and T0AM are electrochemically characterized. T0AM was sensed by means of a glassy carbon electrode; furthermore, T1AM was sensed both with a graphitic surface (oxidatively) as well as with mercury (reductively). For both compounds, after oxidation, it was possible to observe the reversible redox reaction concerning the benzoquinone/hydroquinone couple, thus increasing the specificity of the electroanalysis. Therefore, this work provides the basis for an ‘at-point-of-use’ electrochemical strip test for T1AM and T0AM.

An Open Source BI Approach: Concept Proof Tracking Fleet

É possível assistir nos dias de hoje, a um processo tecnológico evolutivo acentuado por toda a parte do globo. No caso das empresas, quer as pequenas, médias ou de grandes dimensões, estão cada vez mais dependentes dos sistemas informatizados para realizar os seus processos de negócio, e consequentemente à geração de informação referente aos negócios e onde, muitas das vezes, os dados não têm qualquer relacionamento entre si. A maioria dos sistemas convencionais informáticos não são projetados para gerir e armazenar informações estratégicas, impossibilitando assim que esta sirva de apoio como recurso estratégico. Portanto, as decisões são tomadas com base na experiência dos administradores, quando poderiam serem baseadas em factos históricos armazenados pelos diversos sistemas. Genericamente, as organizações possuem muitos dados, mas na maioria dos casos extraem pouca informação, o que é um problema em termos de mercados competitivos. Como as organizações procuram evoluir e superar a concorrência nas tomadas de decisão, surge neste contexto o termo Business Intelligence(BI). A GisGeo Information Systems é uma empresa que desenvolve software baseado em SIG (sistemas de informação geográfica) recorrendo a uma filosofia de ferramentas open-source. O seu principal produto baseia-se na localização geográfica dos vários tipos de viaturas, na recolha de dados, e consequentemente a sua análise (quilómetros percorridos, duração de uma viagem entre dois pontos definidos, consumo de combustível, etc.). Neste âmbito surge o tema deste projeto que tem objetivo de dar uma perspetiva diferente aos dados existentes, cruzando os conceitos BI com o sistema implementado na empresa de acordo com a sua filosofia. Neste projeto são abordados alguns dos conceitos mais importantes adjacentes a BI como, por exemplo, modelo dimensional, data Warehouse, o processo ETL e OLAP, seguindo a metodologia de Ralph Kimball. São também estudadas algumas das principais ferramentas open-source existentes no mercado, assim como quais as suas vantagens/desvantagens relativamente entre elas. Em conclusão, é então apresentada a solução desenvolvida de acordo com os critérios enumerados pela empresa como prova de conceito da aplicabilidade da área Business Intelligence ao ramo de Sistemas de informação Geográfica (SIG), recorrendo a uma ferramenta open-source que suporte visualização dos dados através de dashboards.