Two sources of Michael Polanyi`s prototypal notion of incommensurability: Evans-Pritchard on Azande witchcraft and St Augustine on conversion

Michael Polanyi argues in Personal Knowledge (1958) that conceptual frameworks involved in major scientific controversies are separated by a `logical gap'. Such frameworks, according to Polanyi (1958: 151), are logically disconnected: their protagonists think differently, use different languages and occupy different worlds. Relinquishing one framework and adopting another, Polanyi's scientist undergoes a `conversion' to a new `faith'. Polanyi, in other words, presaged Kuhn and Feyerabend's concept of incommensurability. To what influences was Polanyi subject as he developed his concept of the logical gap? The answer, as unfolded in this article, is twofold: Evans-Pritchard's Witchcraft, Oracles and Magic among the Azande and the Confessions of St Augustine.

A mechanistic study on altered pharmacokinetics of irinotecan by St. Johns wort

Irinotecan (CPT-11) is an important anticancer drug in management of advanced colon cancer. A marked protective effect on CPT-11-induced blood and gastrointestinal toxicity is obtained by combination of St. John's wort (SJW) in recent clinical and rat studies. However, the mechanism is unclear. This study aimed to explore the effects of SJW on the pharmacokinetics of CPT-11 and its major metabolites (SN-38 and SN-38 glucuronide) in rats and the underlying mechanisms using several in vitro models. Short-term (3 days) and long-term (14 days) pretreatment with SJW were conducted in rats to examine the effects of co-administered SJW on the plasma pharmacokinetics of CPT-11, SN-38 and SN- 38 glucuronide. Rat liver microsomes and a rat hepatoma cell line, H4-II-E cells, were utilized to study the effects of aqueous and ethanolic extracts (AE and EE) and major active components (hyperforin, hypericin and quercetin) of SJW on CPT-11 and SN-38 metabolism and intracellular accumulation. Co-administered SJW for consecutive 14 days significantly decreased the initial plasma concentration (C0) of CPT-11, the area under the concentration-time curve (AUC0-10hr) and maximum plasma concentration (Cmax) of SN-38. The ethanolic extracts (EE) of SJW at 5 μ g/ml significantly decreased SN-38 glucuronidation by 45% (P < 0.05) in rat hepatic microsomes. Pre-incubation of aqueous SJW extracts (AE) at 10 g/ml, SJW EE at 5 μg/ml, and quercetin at 10μ M significantly increased the glucuronidation of SN-38 in H4- II-E cells. A 2-hr pre-incubation of quercetin (100μ M) significantly increased the intracellular accumulation of CPT-11 (P < 0.05). However, pre-incubation of hypericin (20 nM and 200 nM) and hyperforin (1μ M) significantly decreased the intracellular accumulation of CPT-11. In addition, pre-incubation of hypericin, SJW EE and quercetin significantly increased the intracellular accumulation of SN-38. Aqueous and ethanolic SJW extracts and its major active components did not alter the plasma protein binding of CPT-11 and SN-38. These results indicated that the aqueous and ethanolic extracts of SJW and its major active components could markedly alter glucuronidation of SN-38 and intracellular accumulation of CPT-11 and SN-38, which probably provides partial explanation for the altered plasma pharmacokinetics of CPT-11 and SN-38 and the antagonizing effects on the toxicities of CPT-11. Further studies are needed to explore the role of both pharmacokinetic and pharmacodynamic components in the protective effect of SJW against the toxicities of CPT-11.

Fitting ST-OWA operators to empirical data

The OWA operators gained interest among researchers as they provide a continuum of aggregation operators able to cover the whole range of compensation between the minimum and the maximum. In some circumstances, it is useful to consider a wider range of values, extending below the minimum and over the maximum. ST-OWA are able to surpass the boundaries of variation of ordinary compensatory operators. Their application requires identification of the weighting vector, the t-norm, and the t-conorm. This task can be accomplished by considering both the desired analytical properties and empirical data.

St. Johns wort attenuates irinotecan-induced diarhea via down-regulation of intestinal pro-inflammatory cytokines and inhibition of intestinal epithelial apoptosis

Diarrhea is a common dose-limiting toxicity associated with cancer chemotherapy, in particular for drugs such as irinotecan (CPT-11), 5-fluouracil, oxaliplatin, capecitabine and raltitrexed. St. John's wort (Hypericum perforatum, SJW) has anti-inflammatory activity, and our preliminary study in the rat and a pilot study in cancer patients found that treatment of SJW alleviated irinotecan-induced diarrhea. In the present study, we investigated whether SJW modulated various pro-inflammatory cytokines including interleukins (IL-1β, IL-2, IL-6), interferon (IFN-γ) and tumor necrosis factor-α (TNF-α) and intestinal epithelium apoptosis in rats. The rats were treated with irinotecan at 60 mg/kg for 4 days in combination with oral SJW or SJW-free control vehicle at 400 mg/kg for 8 days. Diarrhea, tissue damage, body weight loss, various cytokines including IL-1β, IL-2, IL-6, IFN-γ and TNF-α and intestinal epithelial apoptosis were monitored over 11 days. Our studies demonstrated that combined SJW markedly reduced CPT-11-induced diarrhea and intestinal lesions. The production of pro-inflammatory cytokines such as IL-1β, IFN-γ and TNF-α was significantly up-regulated in intestine. In the mean time, combined SJW significantly suppressed the intestinal epithelial apoptosis induced by CPT-11 over days 5–11. In particular, combination of SJW significantly inhibited the expression of TNF-α mRNA in the intestine over days 5–11. In conclusion, inhibition of pro-inflammatory cytokines and intestinal epithelium apoptosis partly explained the protective effect of SJW against the intestinal toxicities induced by irinotecan. Further studies are warranted to explore the potential for STW as an agent in combination with chemotherapeutic drugs to lower their dose-limiting toxicities.

St Johns wort modulates the toxicities and parmacokinetics of CPT-11 (Irontecan) in rats

CPT-11 is a DNA topoisomerase I inhibitor for the therapy of colorectal cancer, whereas St. Johnrsquos Wort (Hypericum perforatum, SJW) is a widely used herbal anti-depressant. This study aimed to investigate the effects of co-administered SJW on the toxicities and pharmacokinetics of CPT-11 and the underlying mechanisms. The body weight loss, gastrointestinal and hematological toxicities induced by CPT-11, and the pharmacokinetic parameters of CPT-11 were evaluated in rats pretreated with SJW or vehicle. Rats treated with CPT-11 alone experienced rapid decrease in body weight, whereas co-administration of SJW with CPT-11 resulted in lesser body weight loss. The gastrointestinal and hematological toxicities following CPT-11 injection were both alleviated in the presence of SJW. The rat pharmacokinetics of both CPT-11 and its metabolite SN-38 were significantly altered in presence of SJW. In conclusion, co-administered SJW significantly ameliorated the toxicities induced by CPT-11. The protective effect of SJW may be partially due to pharmacokinetic interaction between CPT-11 and SJW.

Lost in translation? William Wardell's St John's College, Sydney and Convent and School, Kew

This paper considers two Colleges designed by the nineteenth century architect William Wardell (1823-99): St John’s College, within the University of Sydney (1858-59) and Convent and School, Kew, now known as Genazzano FCJ College Kew, Melbourne (1889). The approach of significant anniversaries for each of the Colleges has been the major impetus behind the current research. Both commissions demonstrate laudable aspirations; difficulty in comprehending and realising the design; partial completions and accretions over time which testify to changes in economic fortune and taste; inappropriate additions; and decades of neglect fuelled by a general misunderstanding of the 19th century for much of the 20th century. At the beginning of the 21st century conservation management plans were commissioned independently for both projects. Using the two Colleges as case studies, this paper examines tradition and its transformation, design and its translation, heritage and its significance.

William Wardell's St John's College within the University of Sydney, 1858-59

Ursula wrote the essay for the catalogue of the Wardell Exhibition.

William Wardell's 1859 St John's College - a rare realisation of Pugin's ideal Catholic College?

William Wardell’s St John’s College, Sydney, considered the grandest and architecturally most distinguished university college in New South Wales, is an exceptional example of 19th century Gothic Revival architecture.  The information board outside the college states that St John’s is ‘a rare realisation of Pugin’s ideal Catholic College’ and further that ‘it demonstrates [Pugin]’s profound influence on the work of Wardell’. This is but a small part of the story. The commission for St John’s College was far more complex.  The correspondence between the architects, William Wardell, Edmund Blacket and others, and St John’s Council indicates that right from the beginning there was a general lack of understanding of Wardell’s original design concept for the building. This has continued to the present day, as evidenced by the information on the board outside St John’s College, in which it is incorrectly assumed that Wardell’s proposal included a quadrangle as featured in Pugin’s ‘ideal College’. This paper, based largely on primary sources, investigates such claims about St John’s, considers William Wardell and the Gothic Revival, examines St John’s College within the University of Sydney – its design and its translation and posits a few conclusions leading to new understandings.