Deliberative assessment of surrogate consent in dementia research

Background Research involving incapacitated persons with dementia entails complex scientific, legal, and ethical issues, making traditional surveys of layperson views on the ethics of such research challenging. We therefore assessed the impact of democratic deliberation (DD), involving balanced, detailed education and peer deliberation, on the views of those responsible for persons with dementia. Methods One hundred and seventy-eight community-recruited caregivers or primary decision-makers for persons with dementia were randomly assigned to either an all-day DD session group or a control group. Educational materials used for the DD session were vetted for balance and accuracy by an interdisciplinary advisory panel. We assessed the acceptability of family-surrogate consent for dementia research (“surrogate-based research”) from a societal policy perspective as well as from the more personal perspectives of deciding for a loved one or for oneself (surrogate and self-perspectives), assessed at baseline, immediately post-DD session, and 1 month after DD date, for four research scenarios of varying risk-benefit profiles. Results At baseline, a majority in both the DD and control groups supported a policy of family consent for dementia research in all research scenarios. The support for a policy of family consent for surrogate-based research increased in the DD group, but not in the control group. The change in the DD group was maintained 1 month later. In the DD group, there were transient changes in attitudes from surrogate or self-perspectives. In the control group, there were no changes from baseline in attitude toward surrogate consent from any perspective. Conclusions Intensive, balanced, and accurate education, along with peer deliberation provided by democratic deliberation, led to a sustained increase in support for a societal policy of family consent in dementia research among those responsible for dementia patients.

Who has rights to what? Inclusion in Australian early childhood programs

In early childhood settings prior to school and in the early years of primary school, debate continues over the meaning of inclusion and its scope in terms of the groups under consideration. The genealogies of early childhood education and care, early primary school, special education and cultural education were examined to identify recurring and emerging approaches to inclusion within Australian programs for children aged birth to eight years. Approaches to inclusion encompassing multiple forms of diversity co-exist in the Australian educational literature with targeted approaches focused on disabilities or risk. These differing approaches reflect underlying ideological divisions and varying assumptions about diversity. Multiple approaches, including the expansion of early childhood services, reflect tensions over children’s rights, conceptualisations of inclusion, expectations of teachers, system coordination, economic constraints and political pressure to cater for a complex range of young children in varied settings. The paper incorporates discussion on underlying philosophical tensions within the early childhood field.

Keeping in constant touch : the predictors of young Australians’ mobile phone involvement

Little is known about the psychological underpinnings of young people’s mobile phone behaviour. In the present research, 292 young Australians, aged 16–24 years, completed an online survey assessing the effects of self-identity, in-group norm, the need to belong, and self-esteem on their frequency of mobile phone use and mobile phone involvement, conceptualised as people’s degree of cognitive and behavioural association with their mobile phone. Structural equation modelling revealed that age (younger) and self-identity significantly predicted the frequency of mobile phone use. In contrast, age (younger), gender (female), self-identity and in-group norm predicted young people’s mobile phone involvement. Neither self-esteem nor the need to belong significantly predicted mobile phone behaviour. The present study contributes to our understanding of this phenomenon and provides an indication of the characteristics of young people who may become highly involved with their mobile phone.

Life on the edge : housing experiences in three remote Australian indigenous settlements

This analysis of housing experiences and aspirations in three remote Indigenous settlements in Australia (Mimili, Maningrida and Palm Island) reveals extreme liveability problems directly related to the scale and form of housing provision. Based upon field visits to each of the settlements and extensive interviews with residents and local housing and community officers, the paper analyses two aspects of living in such housing conditions at two spatial scales, the layout of the settlement and the design of individual houses. The failings at both scales are shown to be the fault of a dysfunctional housing system that is only recently been addressed.

Full circle : the future of sustainable fashion manufacturing in New Zealand

Many fashion businesses in New Zealand have followed a global trend towards inexpensive off shore manufacturing. The transfer of the production of garments to overseas workers has had consequences for the wellbeing of local businesses, fashion designers and garment makers. The gradual decline of fashion manufacturing also appears to have resulted in a local fashion scene where many garments look the same in style, colour, fabric, cut and fit. The excitement of the past, where the majority of fashion designers established their own individuality through the cut and shape of the garments that they produced, may have been inadvertently lost in an effort to take advantage of cost savings achieved through mass production and manufacturing methods which are now largely unavailable in New Zealand. Consequently, a sustainable local fashion and manufacturing industry, with design integrity, seems further out of reach. This paper is focussed upon the thesis that the design and manufacture of a fashion garment, bearing in mind certain economic and practical restrictions at its inception, can contribute to a more sustainable fashion manufacturing industry in New Zealand.

In vitro and in vivo examination of the cell surface glycoprotein CDCP1

A number of reports have demonstrated the importance of the CUB domaincontaining protein 1 (CDCP1) in facilitating cancer progression in animal models and the potential of this protein as a prognostic marker in several malignancies. CDCP1 facilitates metastasis formation in animal models by negatively regulating anoikis, a type of apoptosis triggered by the loss of attachment signalling from cell-cell contacts or cell-extra cellular matrix (ECM) contacts. Due to the important role CDCP1 plays in cancer progression in model systems, it is considered a potential drug target to prevent the metastatic spread of cancers. CDCP1 is a highly glycosylated 836 amino acid cell surface protein. It has structural features potentially facilitating protein-protein interactions including 14 N-glycosylation sites, three CUB-like domains, 20 cysteine residues likely to be involved in disulfide bond formation and five intracellular tyrosine residues. CDCP1 interacts with a variety of proteins including Src family kinases (SFKs) and protein kinase C ä (PKCä). Efforts to understand the mechanisms regulating these interactions have largely focussed on three CDCP1 tyrosine residues Y734, Y743 and Y762. CDCP1-Y734 is the site where SFKs phosphorylate and bind to CDCP1 and mediate subsequent phosphorylation of CDCP1-Y743 and -Y762 which leads to binding of PKCä at CDCP1-Y762. The resulting trimeric protein complex of SFK•CDCP1•PKCä has been proposed to mediate an anti-apoptotic cell phenotype in vitro, and to promote metastasis in vivo. The effect of mutation of the three tyrosines on interactions of CDCP1 with SFKs and PKCä and the consequences on cell phenotype in vitro and in vivo have not been examined. CDCP1 has a predicted molecular weight of ~90 kDa but is usually detected as a protein which migrates at ~135 kDa by Western blot analysis due to its high degree of glycosylation. A low molecular weight form of CDCP1 (LMWCDCP1) of ~70 kDa has been found in a variety of cancer cell lines. The mechanisms leading to the generation of LMW-CDCP1 in vivo are not well understood but an involvement of proteases in this process has been proposed. Serine proteases including plasmin and trypsin are able to proteolytically process CDCP1. In addition, the recombinant protease domain of the serine protease matriptase is also able to cleave the recombinant extracellular portion of CDCP1. Whether matriptase is able to proteolytically process CDCP1 on the cell surface has not been examined. Importantly, proteolytic processing of CDCP1 by trypsin leads to phosphorylation of its cell surface-retained portion which suggests that this event leads to initiation of an intracellular signalling cascade. This project aimed to further examine the biology of CDCP1 with a main of focus on exploring the roles played by CDCP1 tyrosine residues. To achieve this HeLa cells stably expressing CDCP1 or the CDCP1 tyrosine mutants Y734F, Y743F and Y762F were generated. These cell lines were used to examine: • The roles of the tyrosine residues Y734, Y743 and Y762 in mediating interactions of CDCP1 with binding proteins and to examine the effect of the stable expression on HeLa cell morphology. • The ability of the serine protease matriptase to proteolytically process cell surface CDCP1 and to examine the consequences of this event on HeLa cell phenotype and cell signalling in vitro. • The importance of these residues in processes associated with cancer progression in vitro including adhesion, proliferation and migration. • The role of these residues on metastatic phenotype in vivo and the ability of a function-blocking anti-CDCP1 antibody to inhibit metastasis in the chicken embryo chorioallantoic membrane (CAM) assay. Interestingly, biochemical experiments carried out in this study revealed that mutation of certain CDCP1 tyrosine residues impacts on interactions of this protein with binding proteins. For example, binding of SFKs as well as PKCä to CDCP1 was markedly decreased in HeLa-CDCP1-Y734F cells, and binding of PKCä was also reduced in HeLa-CDCP1-Y762F cells. In contrast, HeLa-CDCP1-Y743F cells did not display altered interactions with CDCP1 binding proteins. Importantly, observed differences in interactions of CDCP1 with binding partners impacted on basal phosphorylation of CDCP1. It was found that HeLa-CDCP1, HeLa-CDCP1-Y743F and -Y762F displayed strong basal levels of CDCP1 phosphorylation. In contrast, HeLa-CDCP1-Y734F cells did not display CDCP1 phosphorylation but exhibited constitutive phosphorylation of focal adhesion kinase (FAK) at tyrosine 861. Significantly, subsequent investigations to examine this observation suggested that CDCP1-Y734 and FAK-Y861 are competitive substrates for SFK-mediated phosphorylation. It appeared that SFK-mediated phosphorylation of CDCP1- Y734 and FAK-Y861 is an equilibrium which shifts depending on the level of CDCP1 expression in HeLa cells. This suggests that the level of CDCP1 expression may act as a regulatory mechanism allowing cells to switch from a FAK-Y861 mediated pathway to a CDCP1-Y734 mediated pathway. This is the first time that a link between SFKs, CDCP1 and FAK has been demonstrated. One of the most interesting observations from this work was that CDCP1 altered HeLa cell morphology causing an elongated and fibroblastic-like appearance. Importantly, this morphological change depended on CDCP1- Y734. In addition, it was observed that this change in cell morphology was accompanied by increased phosphorylation of SFK-Y416. This suggests that interactions of SFKs with CDCP1-Y734 increases SFK activity since SFKY416 is critical in regulating kinase activity of these proteins. The essential role of SFKs in mediating CDCP1-induced HeLa cell morphological changes was demonstrated using the SFK-selective inhibitor SU6656. This inhibitor caused reversion of HeLa-CDCP1 cell morphology to an epithelial appearance characteristic of HeLa-vector cells. Significantly, in vitro studies revealed that certain CDCP1-mediated cell phenotypes are mediated by cellular pathways dependent on CDCP1 tyrosine residues whereas others are independent of these sites. For example, CDCP1 expression caused a marked increase in HeLa cell motility that was independent of CDCP1 tyrosine residues. In contrast, CDCP1- induced decrease in HeLa cell proliferation was most prominent in HeLa- CDCP1-Y762F cells, potentially indicating a role for this site in regulating proliferation in HeLa cells. Another cellular event which was identified to require phosphorylation of a particular CDCP1 tyrosine residue is adhesion to fibronectin. It was observed that the CDCP1-mediated strong decrease in adhesion to fibronectin is mostly restored in HeLa-CDCP1-Y743F cells. This suggests a possible role for CDCP1-Y743 in causing a CDCP1-mediated decrease in adhesion. Data from in vivo experiments indicated that HeLa-CDCP1-Y734F cells are more metastic than HeLa-CDCP1 cells in vivo. This indicates that interaction of CDCP1 with SFKs and PKCä may not be required for CDCP1-mediated metastasis formation of HeLa cells in vivo. The metastatic phenotype of these cells may be caused by signalling involving FAK since HeLa-CDCP1- Y734F cells are the only CDCP1 expressing cells displaying constitutive phosphorylation of FAK-Y861. HeLa-CDCP1-Y762F cells displayed a very low metastatic ability which suggests that this CDCP1 tyrosine residue is important in mediating a pro-metastatic phenotype in HeLa cells. More detailed exploration of cellular events occurring downstream of CDCP1-Y734 and -Y762 may provide important insights into the mechanisms altering the metastatic ability of CDCP1 expressing HeLa cells. Complementing the in vivo studies, anti-CDCP1 antibodies were employed to assess whether these antibodies are able to inhibit metastasis of CDCP1 and CDCP1 tyrosine mutants expressing HeLa cells. It was found that HeLa- CDCP1-Y734F cells were the only cell line which was markedly reduced in the ability to metastasise. In contrast, the ability of HeLa-CDCP1, HeLa- CDCP1-Y743F and -Y762F cells to metastasise in vivo was not inhibited. These data suggest a possible role of interactions of CDCP1 with SFKs, occurring at CDCP1-Y734, in preventing an anti-metastatic effect of anti- CDCP1 antibodies in vivo. The proposal that SFKs may play a role in regulating anti-metastatic effects of anti-CDCP1 antibodies was supported by another experiment where differences between HeLa-CDCP1 cells and CDCP1 expressing HeLa cells (HeLa-CDCP1-S) from collaborators at the Scripps Research Institute were examined. It was found that HeLa-CDCP1-S cells express different SFKs than CDCP1 expressing HeLa cells generated for this study. This is important since HeLa-CDCP1-S cells can be inhibited in their metastatic ability using anti-CDCP1 antibodies in vivo. Importantly, these data suggest that further examinations of the roles of SFKs in facilitating anti-metastatic effects of anti-CDCP1 antibodies may give insights into how CDCP1 can be blocked to prevent metastasis in vivo. This project also explored the ability of the serine protease matriptase to proteolytically process cell surface localised CDCP1 because it is unknown whether matriptase can cleave cell surface CDCP1 as it has been reported for other proteases such as trypsin and plasmin. Furthermore, the consequences of matriptase-mediated proteolysis on cell phenotype in vitro and cell signalling were examined since recent reports suggested that proteolysis of CDCP1 leads to its phosphorylation and may initiate cell signalling and consequently alter cell phenotype. It was found that matriptase is able to proteolytically process cell surface CDCP1 at low nanomolar concentrations which suggests that cleavage of CDCP1 by matriptase may facilitate the generation of LWM-CDCP1 in vivo. To examine whether matriptase-mediated proteolysis induced cell signalling anti-phospho Erk 1/2 Western blot analysis was performed as this pathway has previously been examined to study signalling in response to proteolytic processing of cell surface proteins. It was found that matriptase-mediated proteolysis in CDCP1 expressing HeLa cells initiated intracellular signalling via Erk 1/2. Interestingly, this increase in phosphorylation of Erk 1/2 was also observed in HeLa-vector cells. This suggested that initiation of cell signalling via Erk 1/2 phosphorylation as a result of matriptase-mediated proteolysis occurs by pathways independent of CDCP1. Subsequent investigations measuring the flux of free calcium ions and by using a protease-activated receptor 2 (PAR2) agonist peptide confirmed this hypothesis. These data suggested that matriptase-mediated proteolysis results in cell signalling via a pathway induced by the activation of PAR2 rather than by CDCP1. This indicates that induction of cell signalling in HeLa cells as a consequence of matriptase-mediated proteolysis occurs via signalling pathways which do not involve phosphorylation of Erk 1/2. Consequently, it appears that future attempts should focus on the examination of cellular pathways other than Erk 1/2 to elucidate cell signalling initiated by matriptase-mediated proteolytic processing of CDCP1. The data presented in this thesis has explored in vitro and in vivo aspects of the biology of CDCP1. The observations summarised above will permit the design of future studies to more precisely determine the role of CDCP1 and its binding partners in processes relevant to cancer progression. This may contribute to further defining CDCP1 as a target for cancer treatment.

Youth theatre and the articulation of cultural capital : refocusing Bourdieu through ethnography

This study of working-class and middle-class youth theatre workshops examines the processes through which this cultural form is appropriated by different class groups. Whereas the middle-class workshop proceeded efficiently and harmoniously, the working-class group resisted a number of institutional constraints traditionally associated with play rehearsal and performance. The processes of such symbolic struggle in the working-class group appeared to differ from Bourdieu's account of cultural domination. The article explores the explanatory contribution of the ethnographic case study to the analysis of the class basis of cultural tastes and practices and suggest that Bourdieu's account of class relations would gain from inclusion of this level of analysis. The situated study of the youth theatre workshops suggests that at this level, there is possibly more scope for symbolic struggle between the classes than was found by Bourdieu.

Train service timetabling in railway open markets by particle swarm optimisation

Railway timetabling is an important process in train service provision as it matches the transportation demand with the infrastructure capacity while customer satisfaction is also considered. It is a multi-objective optimisation problem, in which a feasible solution, rather than the optimal one, is usually taken in practice because of the time constraint. The quality of services may suffer as a result. In a railway open market, timetabling usually involves rounds of negotiations among a number of self-interested and independent stakeholders and hence additional objectives and constraints are imposed on the timetabling problem. While the requirements of all stakeholders are taken into consideration simultaneously, the computation demand is inevitably immense. Intelligent solution-searching techniques provide a possible solution. This paper attempts to employ a particle swarm optimisation (PSO) approach to devise a railway timetable in an open market. The suitability and performance of PSO are studied on a multi-agent-based railway open-market negotiation simulation platform.

Planning for knowledge based urban development in Malaysia : Cyberjaya @ Multimedia Super Corridor

Knowledge based urban development (KBUD) is a new paradigm in urban planning tailoring to the era of knowledge economy. It aims mainly to assist a contemporary city to promote a more sustainable socio-spatial order. The paper reports on the investigation of KBUD initiative in Malaysia which is manifested through the establishment of a project called Multimedia Super Corridor (MSC). MSC Malaysia aims to attract knowledge workers and industries to invest and operate within the area by creating a world class urban corridor with state-of-the-art multimedia infrastructure, efficient transportation system and an attractive living environment. Based on documents analysis and interviews, this paper analyses the strategies, implementations, and achievements of KBUD initiative in Cyberjaya, being the leading intelligent city of the unique Malaysia’s KBUD project-MSC Malaysia. A critical evaluation is made to assess the achievements of MSC, by looking at the physical changes after about ten years since its official launching. The findings recommend some valuable lessons for other cities that strive to develop KBUD strategies, strengthen their sustainable socio-spatial policies, and seek a global recognition.

Attractive subfamilies of BLS curves for implementing high-security pairings

Barreto-Lynn-Scott (BLS) curves are a stand-out candidate for implementing high-security pairings. This paper shows that particular choices of the pairing-friendly search parameter give rise to four subfami- lies of BLS curves, all of which offer highly efficient and implementation- friendly pairing instantiations. Curves from these particular subfamilies are defined over prime fields that support very efficient towering options for the full extension field. The coefficients for a specific curve and its correct twist are automat-ically determined without any computational effort. The choice of an extremely sparse search parameter is immediately reflected by a highly efficient optimal ate Miller loop and final exponentiation. As a resource for implementors, we give a list with examples of implementation-friendly BLS curves through several high-security levels.

Deep Raman spectroscopy for the non-invasive standoff detection of concealed chemical threat agents

Deep Raman spectroscopy has been utilized for the standoff detection of concealed chemical threat agents from a distance of 15 meters under real life background illumination conditions. By using combined time and space resolved measurements, various explosive precursors hidden in opaque plastic containers were identified non-invasively. Our results confirm that combined time and space resolved Raman spectroscopy leads to higher selectivity towards the sub-layer over the surface layer as well as enhanced rejection of fluorescence from the container surface when compared to standoff spatially offset Raman spectroscopy. Raman spectra that have minimal interference from the packaging material and good signal-to-noise ratio were acquired within 5 seconds of measurement time. A new combined time and space resolved Raman spectrometer has been designed with nanosecond laser excitation and gated detection, making it of lower cost and complexity than picosecond-based laboratory systems.

GATEKEEPING, GATEWATCHING, REALIMENTAÇÃO EM TEMPO REAL: novos desafios para o Jornalismo

Faz vários anos que se sabe como os blogueiros e outros comentaristas on-line independentes criticam, corrigem, e de outra maneira desafiam o jornalismo convencional, porém isto ainda não foi plenamente aceito pelos jornalistas; as hostilidades entre as empresas de mídia e a nova geração de jornalistas cidadãos continuam a irromper de vez em quando. O antigo monopólio de gatekeeping mantido pela mídia de massa tem sido desafiado pela nova prática de gatewatching: feita pelos blogueiros individuais e pelas comunidades de comentaristas que podem não fazer reportagem das notícias de primeira mão, porém fazem a curation e avaliam as notícias e outras informações fornecidas pelas fontes oficiais, e assim prestam um serviço importante. E isto ocorre atualmente com cada vez mais rapidez, quase em tempo real: usando as redes sociais mais recentes, que divulgam, compartilham, comentam, questionam e desacreditam as matérias noticiosas dentro de minutos, e usando plataformas adicionais que possibilitam a colaboração ad hoc rápida e eficaz entre os usuários. Quando centenas de voluntários podem provar dentro de alguns poucos dias que um ministro alemão foi culpado de plágio sério, quando o mundo inteiro fica sabendo de terremotos e tsunamis pelo Twitter – como é que o jornalismo consegue acompanhar tudo isto?