Anti-GnRH antibodies can induce castrate levels of testosterone in patients with advanced prostate cancer

D17DT consists of the GnRH decapeptide linked to diphtheria toxoid. The aim of this pilot study was to assess the tolerance of D17DT and the production of anti-GnRH antibodies from two doses, 30 and 100 μg, in patients with locally advanced prostate cancer. Twelve patients with histologically proven prostate cancer in whom hormonal therapy was indicated were recruited. Patients received either 30 or 100 μg given intramuscularly on three separate occasions over six weeks. Patients were followed up and blood was taken for estimation of serum testosterone, PSA and anti-GnRH antibody titre. Overall the drug was well tolerated. In 5 patients a significant reduction in serum testosterone and PSA was seen. Castrate levels of testosterone were achieved in 4 and maintained for up to 9 months. Patients with the highest antibody titre had the best response in terms of testosterone suppression. This study shows that it is possible to immunize a patient with prostate cancer against GnRH to induce castrate levels of testosterone. This state appears to be reversible. This novel form of immunotherapy may have advantages over conventional forms of hormonal therapy and further studies are warranted in order to try and increase the proportion of responders. © 2000 Cancer Research Campaig

Urinary metabotype of severe asthma evidences decreased carnitine metabolism independent of oral corticosteroid treatment in the U-BIOPRED study

Introduction Asthma is a heterogeneous disease with poorly defined phenotypes. Patients with severe asthma often receive multiple treatments including oral corticosteroids (OCS). Treatment may modify the observed metabotype, rendering it challenging to investigate underlying disease mechanisms. Here, we aimed to identify dysregulated metabolic processes in relation to asthma severity and medication. Methods Baseline urine was collected prospectively from healthy participants (n=100), patients with mild-to-moderate asthma (n=87) and patients with severe asthma (n=418) in the cross-sectional U-BIOPRED cohort; 12–18-month longitudinal samples were collected from patients with severe asthma (n=305). Metabolomics data were acquired using high-resolution mass spectrometry and analysed using univariate and multivariate methods. Results A total of 90 metabolites were identified, with 40 significantly altered (p<0.05, false discovery rate <0.05) in severe asthma and 23 by OCS use. Multivariate modelling showed that observed metabotypes in healthy participants and patients with mild-to-moderate asthma differed significantly from those in patients with severe asthma (p=2.6×10−20), OCS-treated asthmatic patients differed significantly from non-treated patients (p=9.5×10−4), and longitudinal metabotypes demonstrated temporal stability. Carnitine levels evidenced the strongest OCS-independent decrease in severe asthma. Reduced carnitine levels were associated with mitochondrial dysfunction via decreases in pathway enrichment scores of fatty acid metabolism and reduced expression of the carnitine transporter SLC22A5 in sputum and bronchial brushings. Conclusions This is the first large-scale study to delineate disease- and OCS-associated metabolic differences in asthma. The widespread associations with different therapies upon the observed metabotypes demonstrate the need to evaluate potential modulating effects on a treatment- and metabolite-specific basis. Altered carnitine metabolism is a potentially actionable therapeutic target that is independent of OCS treatment, highlighting the role of mitochondrial dysfunction in severe asthma

The Theory of Proportion in Architecture

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Involving Young People in research: Lessons from the 10 MMM Project in South Western Victoria

The paper outlines the 10MMM (Multi-Media Mayhem across 10 towns) project which commenced in 2002 in Southern Grampians Shire in rural Victoria. The project is an interagency initiative aimed at decreasing social isolation and stimulating the expression of a youth voice through multimedia tools (Brumby et al. 2007). It is a participatory research project involving children and young people (aged 12-20) with RMIT University staff involved as mentors and observers. The paper focuses in particular on the 2007-08 Your Say report as part of the Rural Young People, Technology and Wellbeing research project (Marshall et al. 2008), and on the issues raised by the involvement of young people as researchers in the project. The report focused on how young people&#039;s aspirations and social relationships are impacted by technology. The results of the Your Say survey questioned some of the conventional wisdom surrounding use of information and communication technology (ICT). The survey was undertaken by a group of young people who designed and implemented the survey. The training of young people as researchers raised some challenges: the ways cultural codes were managed, the extent of empowerment that took place, the benefits and limitations of using young people as researchers with extensive control over the project (e.g. related to validity of data), and strategies for implementing the current (final) phase of the project. There are important learnings that have occurred in this project, and the paper explores what worked and didn&#039;t work in 10MMM and how the key issues relating to the involvement of young people in research have been addressed

Computers in second/foreign language learning: what is usable for what?

In education, there seems to be a large number of misconceptions about the precise role of the computer and an equal multitude of acronyms which have been developed. The term 'Computer Assisted Language Learning' (CALL with two types of pronunciations as in 'calling' or 'California') seems to be the commonest acronym, "...to describe the use of computers as part of a language course" however with a bias towards the teaching/learning aspect (Hardisty & Windeatt 1989:5). 'Computer Assisted Language' (CALa, the small 'a' to indicate the difference from Computer Assisted Learning CAL) - could be another acronym in the already existed long list which leaves the teaching/learning aspect of the process open. CALa could be divided (in relation to the British tradition of the Communicative Methodology) into four stages:(a) Computer Assisted Language Presentation (CALP), in which the target language (appropriate to the situation) is presented with CALAH (=Computer Assisted Language Awareness Heightening, Scholfield, 1991) features.(b) Computer Assisted Language Learning (CALL), in which the target language (appropriate to the situation) is practised by repetition of the language or drilling of a key phenomenon (with CALAH features).(c) Computer Assisted Language Use (CALU), in which the language (appropriate tothe situation) is used in role-plays or simulations. The computer here could also be used as a database to give feedback on the role-play if needed.(d) Computer Assisted Language Testing (CALTest ), in which the language (appropriate to the situation) is tested.Categorising CALa software, is not an easy task as: (a) the categories do not seem to be clear-cut, as many items could appear in more than one category, and (b) recent hardware/software developrpent brought about novel items which could have a CALa application and need to be categorised. Our attempt is to provide one such categorisation: (a) including all three (existing) types of categorising CALa, (b) relating each applicatiοn with a CALa activity which we think the item could make a contribution to, and (c) categorising the items according to the ease of use keeping the language ~ teacher in mind, and thus separate: (a) Dedicated CALa, with straight forward use for the uninitiated language teacher, and often designed with CALa activities in mind (b) Non-dedicated CALa, designed initially for other applications, with possible language teaching/learning functions and which usuually requires some previous knowledge either of computers or of computer programs