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.

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.

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.

Method for determining reaction rate of mild steel containers during melting of magnesium-aluminium alloys and effect of aluminium content on directionally solidified microstructures

A magnesium alloy of eutectic composition (33 wt-'%Al) was directionally solidified in mild steel tubes at two growth rates, 32 and 580 mum s(-1,) in a temperature gradient between 10 and 20 K mm(-1). After directional solidification, the composition of each specimen varied dramatically, from 32'%Al in the region that had remained solid to 18%Al (32 mum s(-1) specimen) and 13%Al (580 mum s(-1) specimen) at the plane that had been quenched from the eutectic temperature. As the aluminium content decreased, the microstructure contained an increasing volume fraction of primary magnesium dendrites and the eutectic morphology gradually changed from lamellar to partially divorced. The reduction in aluminium content was caused by the growth of an Al-Fe phase ahead of the Mg-Al growth front. Most of the growth of the Al-Fe phase occurred during the remelting period before directional solidification. The thickness of the Al-Fe phase increased with increased temperature and time of contact with the molten Mg-Al alloy. (C) 2003 Maney Publishing.

After hMSH2 and hMLH1- what next? Analysis of three-generational, population-based, early-onset colorectal cancer families

The aim of our study was to examine the role of genetic factors on early-onset colorectal cancer after excluding the impact of germline mutations in the two major mismatch repair genes. A total of 131 incident probands, under 45 years at diagnosis of a first primary colorectal cancer selected from the Victorian Cancer Registry, and their first-and second-degree relatives, were interviewed. Germline DNA from all 12 probands with a family history meeting the modified Amsterdam Criteria for Hereditary Non-Polyposis Colorectal Cancer (HNPCC) and a random sample of 31 of the remaining probands was screened for mutations in hMSH2 and hMLH1 via manual sequencing. Germline mutations were identified in 6 of the 131 probands (5%), all from the "HNPCC" families. Of the remaining 125 probands, 51 (41%) reported at least one first-or second-degree relative with colorectal cancer with an excess of colorectal cancer in first-degree relatives (SMR = 2.7, 95% CI = 1.7-4.1, p < 0.001). The lifetime risk to age 70 for first-degree relatives was 8.0% (5.0-12.8%), compared to the Victorian population risk of 3.2% (p = 0.01). The best fitting major gene model was a recessively-inherited risk of 98% to age 70 (95% CI = 24-100%) carried by 0.17% of the population and would explain 15% of all colorectal cancer in cases with a diagnosis before age 45. Early-onset colorectal cancer is strongly familial even after excluding families found to be segregating a mutation in either of the 2 major mismatch repair genes. There is evidence for a role of yet to be identified genes associated with a high recessively-inherited risk of colorectal cancer.

Herb-drug interactions: a literature review

Herbs are often administered in combination with therapeutic drugs, raising the potential of herb-drug interactions. An extensive review of the literature identified reported herb-drug interactions with clinical significance, many of which are from case reports and limited clinical observations.
Cases have been published reporting enhanced anticoagulation and bleeding when patients on long-term warfarin therapy also took Salvia miltiorrhiza (danshen). Allium sativum (garlic) decreased the area under the plasma concentration-time curve (AUC) and maximum plasma concentration of saquinavir, but not ritonavir and paracetamol (acetaminophen), in volunteers. A. sativum increased the clotting time and international normalised ratio of warfarin and caused hypoglycaemia when taken with chlorpropamide. Ginkgo biloba (ginkgo) caused bleeding when combined with warfarin or aspirin (acetylsalicylic acid), raised blood pressure when combined with a thiazide diuretic and even caused coma when combined with trazodone in patients. Panax ginseng (ginseng) reduced the blood concentrations of alcohol (ethanol) and warfarin, and induced mania when used concomitantly with phenelzine, but ginseng increased the efficacy of influenza vaccination. Scutellaria baicalensis (huangqin) ameliorated irinotecan-induced gastrointestinal toxicity in cancer patients.
Piper methysticum (kava) increased the 'off' periods in patients with parkinsonism taking levodopa and induced a semicomatose state when given concomitantly with alprazolam. Kava enhanced the hypnotic effect of alcohol in mice, but this was not observed in humans. Silybum marianum (milk thistle) decreased the trough concentrations of indinavir in humans. Piperine from black (Piper nigrum Linn) and long (P. longum Linn) peppers increased the AUC of phenytoin, propranolol and theophylline in healthy volunteers and plasma concentrations of rifamipicin (rifampin) in patients with pulmonary tuberculosis. Eleutheroccus senticosus (Siberian ginseng) increased the serum concentration of digoxin, but did not alter the pharmacokinetics of dextromethorphan and alprazolam in humans. Hypericum perforatum (hypericum; St John's wort) decreased the blood concentrations of ciclosporin (cyclosporin), midazolam, tacrolimus, amitriptyline, digoxin, indinavir, warfarin, phenprocoumon and theophylline, but did not alter the pharmacokinetics of carbamazepine, pravastatin, mycophenolate mofetil and dextromethorphan. Cases have been reported where decreased ciclosporin concentrations led to organ rejection. Hypericum also caused breakthrough bleeding and unplanned pregnancies when used concomitantly with oral contraceptives. It also caused serotonin syndrome when used in combination with selective serotonin reuptake inhibitors (e.g. sertraline and paroxetine).
In conclusion, interactions between herbal medicines and prescribed drugs can occur and may lead to serious clinical consequences. There are other theoretical interactions indicated by preclinical data. Both pharmacokinetic and/or pharmacodynamic mechanisms have been considered to play a role in these interactions, although the underlying mechanisms for the altered drug effects and/or concentrations by concomitant herbal medicines are yet to be determined. The clinical importance of herb-drug interactions depends on many factors associated with the particular herb, drug and patient. Herbs should be appropriately labeled to alert consumers to potential interactions when concomitantly used with drugs, and to recommend a consultation with their general practitioners and other medical carers.

Colorectal cancer screening in Australia: an economic evaluation of a potential biennial screening program using faecal occult blood tests

Objective: To evaluate whether the introduction of a national, co-ordinated screening program using the faecal occult blood test represents 'value-for-money' from the perspective of the Australian Government as third-party funder.  Methods: The annual equivalent costs and consequences of a   biennial screening program in 'steady-state' operation were estimated for the Australian population using 1996 as the reference year. Disability-adjusted life years (DALYs) and the years of life lost (YLLs) averted, and the health service costs were modelled, based on the epidemiology and the costs of colorectal cancer in Australia together with the mortality reduction achieved in randomised controlled trials. Uncertainty in the model was examined using Monte Carlo simulation methods. Results: We estimate a minimum or 'base program' of screening those aged 55 to 69 years could avert 250 deaths per annum (95% uncertainty interval 99–400), at a gross cost of $A55 million (95% UI $A46 million to $A96 million) and a gross incremental cost-effectiveness ratio of $A17,000/DALY (95% UI $A13,000/DALY to $A52,000/DALY). Extending the program to include 70 to 74-year-olds is a more effective option (cheaper and higher health gain) than including the 50 to 54-year-olds. Conclusions: The findings of this study support the case for a national program directed at the 55 to 69-year-old age group with extension to 70 to 74-year-olds if there are sufficient resources. The pilot tests recently announced in Australia provide an important opportunity to consider the age range for screening and the sources of uncertainty, identified in the modelled evaluation, to assist decisions on implementing a full national program.

Futures in education

Futures education (FE) in a rapidly changing world is critical if young people are to be empowered to be proactive rather than reactive about the future. Research into young people's images and ideas of the future lead to the disturbing conclusion that, for many, the future is a depressing and fearful place where they feel hopeless and disempowered. On the other hand, as Richard Slaughter writes, 'young people are passionately interested in their own futures, and that of the society in which they live. They universally 'jump at the chance to study something with such intrinsic interest that also intersects with their own life interests in so many ways'. FE explicitly attempts to build on this interest and counter these fears by offering a profound and empowering set of learning strategies and ideas that can help people think and act critically and creatively about the future, without necessarily trying to predict it. Futures educators have, over the past decades, developed useful tools, ideas and a language for use with students of all ages to enable them to develop foresight literacy. Most of us tend to view the future as somehow beyond the present and rarely consider how decisions and choices made today profoundly affect not just one fixed future but any number of futures. The underlying goal of FE is to move from the idea of a single, pre-determined future to that of many possible futures, so that students begin to see that they can determine the future, that they need not be reactive and that they are not powerless. How does one do that? Ideas include, but are not limited to: timelines and Y-diagrams, futures wheels and mind maps, and 'Preferable, possible and probable' futures - a.k.a. the 3Ps. Current Australian curricula present education about the future in various implicit or explicit guises. A plethora of statements and curriculum outcomes mention the future, but essentially take 'it' for granted, and are uninformed by FE literature, language, ideas or tools. Science, the humanities and technology tend to be the main areas where such an implicit futures focus can be found. It also appears in documents about vocational education, civics and lifelong learning. Explicit FE is, as Beare and Slaughter put it, still the missing dimension in education. Explicit FE attempts to develop futures literacy, and draws widely upon futures studies literature for processes and content. FE provides such a wide range of ideas and tools that it can be incorporated into education in any number of ways. Programs in two very different schools, one primary and one secondary, are described in this article to provide examples of some of these ways. The first school, Kimberley Park State Primary School in Brisbane, operates with multi-age classrooms based on a 'thinking curriculum' developed around four organisers: change, perspectives, interconnectedness and sustainability. The second school, St John's Grammar School in Adelaide, is an independent school where FE operates as an integrated approach in Year Seven, as a separate one-semester subject in Year Nine and in separate subjects at other levels. Teachers both at Kimberley Park and St John's are very positive about FE. They say it promotes valuable and authentic learning, assists students to realise they have choices that matter and helps them see that the future need not be all doom and gloom. Because students are interested in the Big Questions, as one teacher put it, FE provides a perfect opportunity to address them, and to consider values that are fundamental for them and the future of the planet. Like any innovation, the long-term success of FE in schools depends on an embedding process so that the innovation does not depend on the enthusiasm and energy of a few individuals, only to disappear when they move on. It requires strong leadership, teacher knowledge, support and enthusiasm, and the support and understanding of the wider school community.

Solidification of cast magnesium alloys

A description of the key solidification steps in the formation of the as-cast microstructure of magnesium alloys is presented. The focus is on the two common magnesium alloy groups: Mg-Al alloys and Mg-Zn-rare earth alloys. The key elements described are: nucleation (including grain refinement), growth of the primary phase and the formation of the eutectic phases. In addition the effect of casting process (e.g. high-pressure diecasting and sand casting) on the outcomes from solidification are discussed. This includes consideration of the formation of banded defects during solidification in the dynamic environment of high pressure die casting.

Grain refinement of pure magnesium using rolled Zirmax® master alloy (MG-33.3ZR)

Owing to the limited solubility of zirconium in molten magnesium, almost all of the zirconium contained in the Zirmax® master alloy (Mg-33.3Zr) is present in the form of nearly pure zirconium particles. Of them, zirconium particle clusters and individual zirconium particles greater than 5

Kristevan aesthetics, performativity and the production of situated knowledge

In this paper, I will draw on the work of Julia Kristeva to argue that performativity can be understood in terms of a materialist ontology that underpins creative production and the knowing subject. To understand this, we need to examine the relationship between individual history, biology and culture and processes through which creative practice attributes value by translating psychic representations of affect and drive into verbal and visual signs. Kristeva's aesthetics does not plunge us into an obscure metaphysics, but provides a model for articulating material-discursive practices that emerge from corporeal responses. Enactments, predicated by desire give rise to agency and judgement allowing practice to test theory through the production of situated knowledge.

Kristeva's psychoanalytical position reveals the necessity of linking material and individual practices of art with the social through language and interpretation. Material-discursive practices can only acquire meaning through their relationship between the speaking subject and addressees. Art itself provides us with the means for discovering the knowledge it produces. In and through material practice, the work of art is capable of transferring back to the artist as viewer, structures of meaning that have hitherto been hidden. In practice, this involves a constant movement between the biological self (the self as 'other') and the social self, the ego. In artistic research, it can be said that the first addressee is the artist her/himself, as social other. Constant movement between the two in creative practice can thus be understood as a performative production of knowledge.