In vivo knockdown of the androgen receptor results in growth inhibition and regression of well-established, castration-resistant prostate tumours

Purpose: Progression to the castration-resistant state is the incurable and lethal end stage of prostate cancer, and there is strong evidence that androgen receptor (AR) still plays a central role in this process. We hypothesize that knocking down AR will have a major effect on inhibiting growth of castration-resistant tumors. Experimental Design: Castration-resistant C4-2 human prostate cancer cells stably expressing a tetracycline-inducible AR-targeted short hairpin RNA (shRNA) were generated to directly test the effects of AR knockdown in C4-2 human prostate cancer cells and tumors. Results:In vitro expression of AR shRNA resulted in decreased levels of AR mRNA and protein, decreased expression of prostate-specific antigen (PSA), reduced activation of the PSA-luciferase reporter, and growth inhibition of C4-2 cells. Gene microarray analyses revealed that AR knockdown under hormone-deprived conditions resulted in activation of genes involved in apoptosis, cell cycle regulation, protein synthesis, and tumorigenesis. To ensure that tumors were truly castration-resistant in vivo, inducible AR shRNA expressing C4-2 tumors were grown in castrated mice to an average volume of 450 mm3. In all of the animals, serum PSA decreased, and in 50% of them, there was complete tumor regression and disappearance of serum PSA. Conclusions: Whereas castration is ineffective in castration-resistant prostate tumors, knockdown of AR can decrease serum PSA, inhibit tumor growth, and frequently cause tumor regression. This study is the first direct evidence that knockdown of AR is a viable therapeutic strategy for treatment of prostate tumors that have already progressed to the castration-resistant state.

Video-stimulated accounts: Young children accounting for interactional matters in front of peers

Research in the early years places increasing importance on participatory methods to engage children. The playback of video-recording to stimulate conversation is a research method that enables children’s accounts to be heard and attends to a participatory view. During video-stimulated sessions, participants watch an extract of video-recording of a specific event in which they were involved, and then account for their participation in that event. Using an interactional perspective, this paper draws distinctions between video-stimulated accounts and a similar research method, popular in education, that of video-stimulated recall. Reporting upon a study of young children’s interactions in a playground, video-stimulated accounts are explicated to show how the participants worked toward the construction of events in the video-stimulated session. This paper discusses how the children account for complex matters within their social worlds, and manage the accounting of others in the video-stimulated session. When viewed from an interactional perspective and used alongside fine grained analytic approaches, video-stimulated accounts are an effective method to provide the standpoint of the children involved and further the competent child paradigm.

Observation of the suppression of water uptake by marine particles

A 4 week intensive measurement campaign was conducted in March–April 2007 at Agnes Water, a remote coastal site on the east coast of Australia. A Volatility-Hygroscopicity-Tandem Differential Mobility Analyser (VH-TDMA) was used to investigate changes in the hygroscopic properties of ambient particles as volatile components were progressively evaporated. Nine out of 18 VH-TDMA volatility scans detected internally mixed multi-component particles in the nucleation and Aitken modes in clean marine air. Evaporation of a volatile, organic-like component in the VH-TDMA caused significant increases in particle hygroscopicity. In 3 scans the increase in hygroscopicity was so large it was explained by an increase in the absolute volume of water uptake by the particle residuals, and not merely an increase in their relative hygroscopicity. This indicates the presence of organic components that were suppressing the hygroscopic growth of mixed particles on the timescale of humidification in the VH-TDMA (6.5 secs). This observation was supported by ZSR calculations for one scan, which showed that the measured growth factors of mixed particles were up to 18% below those predicted assuming independent water uptake of the individual particle components. The observed suppression of water uptake could be due to a reduced rate of hygroscopic growth caused by the presence of organic films or organic-inorganic interactions in solution droplets that had a negative effect on hygroscopicity.

Child participation in the early years : challenges for education

The view that children should have a say in and participate in the decision-making of, matters that affect them is now an accepted position when considering research and policy in the early years. This paper reviews the field of child participation in the Australian context to show that, despite growing evidence of support within policy and research arenas, young children’s participation rights in Australia have not been key agenda items for early childhood education. While a significant part of children’s daily experience takes place in classrooms, the actual practices of engaging young children as participants in everyday activities remains a challenge for early childhood education. Participation is an interactional process that involves managing relationships between children and adults. Recommendations include further research into the daily experiences of young children to show what participation might look like when translated to the everyday activities of the classroom and playground.

Monitoring children's progress using child portfolios

Introduces a method to early childhood professionals of observing children as they are involved in everyday play episodes, record children's development and plan for this, while utilising the knowledge and input of the key players in the partnership, parents and teachers.

Book review : Kellett, M (2010) Rethinking children and research : attitudes in contemporary society

Rethinking Children and Research characterizes Mary Kellett’s vision as campaigner and sociologist actively working for and with children for many years. The book itself is not only visionary; it is informative, thought provoking and pragmatic. From a contemporary standpoint, the manuscript presents a detailed synopsis of the shifts in thinking about research with children and provides an appraisal of the theoretical movements that have driven a participatory research agenda. A strong theoretical approach of the combined lenses of sociologies of childhood and rights discourse is introduced early in the book. From the outset, the reader receives loud and clear, the key message of the book: that children in research should and can be included as competent members who lead research in the study of their everyday lives. The argument for a more mutual research approach is shaped throughout the book using research examples and practical suggestions on how this might be achieved. Overall, the reader is left feeling compelled to adopt such an approach.

Investigating child participation in the everyday talk of teacher and children in a preparatory year

In early years research, policy and education, a democratic perspective that positions children as participants and citizens is increasingly emphasized. These ideas take seriously listening to children’s opinions and respecting children’s influence over their everyday affairs. While much political and social investment has been paid to the inclusion of participatory approaches little has been reported on the practical achievement of such an approach in the day to day of early childhood education within school settings. This paper investigates talk and interaction in the everyday activities of a teacher and children in an Australian preparatory class (for children age 4-6 years) to see how ideas of child participation are experienced. We use an interactional analytic approach to demonstrate how participatory methods are employed in practical ways to manage routine interactions. Analysis shows that whilst the teacher seeks the children’s opinion and involves them in decision-making, child participation is at times constrained by the context and institutional categories of “teacher” and “student” that are jointly produced in their talk. The paper highlights tensions that arise for teachers as they balance a pedagogical intent of “teaching” and the associated institutional expectations, with efforts to engage children in decision-making. Recommendations include adopting a variety of conversational styles when engaging with children; consideration of temporal concerns and the need to acknowledge the culture of the school.

“What’s going on here?” The pedagogy of a data analysis session

Data analysis sessions are a common feature of discourse analytic communities, often involving participants with varying levels of expertise to those with significant expertise. Learning how to do data analysis and working with transcripts, however, are often new experiences for doctoral candidates within the social sciences. While many guides to doctoral education focus on procedures associated with data analysis (Heath, Hindmarsh, & Luff, 2010; McHoul & Rapley, 2001; Silverman, 2011; Wetherall, Taylor, & Yates, 2001), the in situ practices of doing data analysis are relatively undocumented. This chapter has been collaboratively written by members of a special interest research group, the Transcript Analysis Group (TAG), who meet regularly to examine transcripts representing audio- and video-recorded interactional data. Here, we investigate our own actual interactional practices and participation in this group where each member is both analyst and participant. We particularly focus on the pedagogic practices enacted in the group through investigating how members engage in the scholarly practice of data analysis. A key feature of talk within the data sessions is that members work collaboratively to identify and discuss ‘noticings’ from the audio-recorded and transcribed talk being examined, produce candidate analytic observations based on these discussions, and evaluate these observations. Our investigation of how talk constructs social practices in these sessions shows that participants move fluidly between actions that demonstrate pedagogic practices and expertise. Within any one session, members can display their expertise as analysts and, at the same time, display that they have gained an understanding that they did not have before. We take an ethnomethodological position that asks, ‘what’s going on here?’ in the data analysis session. By observing the in situ practices in fine-grained detail, we show how members participate in the data analysis sessions and make sense of a transcript.

Children’s strategies for making friends when starting school

Starting school is a critical and potentially stressful time for many young children, and having supportive relationships with parents, teachers and peers and friends offer better outcomes for school adjustment and social relationships. This paper explores matters of friendship when young children are starting school, and how they initiate friendships. In audio-recorded conversations with a researcher and their peers, the children proposed a number of strategies, including making requests, initiating clubs and teams, and peer intervention to support a friend. Their accounts drew on social knowledge and relational understandings, and showed that having someone, a friend, to play with was important for starting school. Children gave serious attention to developing strategies to initiate friendships.

Investigation of the effect of organics on the water uptake of marine aerosols

Water uptake refers to the ability of atmospheric particles to take up water vapour from the surrounding atmosphere. This is an important property that affects particle size and phase and therefore influences many characteristics of aerosols relevant to air quality and climate. However, the water uptake properties of many important atmospheric aerosol systems, including those related to the oceans, are still not fully understood. Therefore, the primary aim of this PhD research program was to investigate the water uptake properties of marine aerosols. In particular, the effect of organics on marine aerosol water uptake was investigated. Field campaigns were conducted at remote coastal sites on the east coast of Australia (Agnes Water; March-April 2007) and west coast of Ireland (Mace Head; June 2007), and laboratory measurements were performed on bubble-generated sea spray aerosols. A combined Volatility-Hygroscopicity-Tandem Differential Mobility Analyser (VH-TDMA) was employed in all experiments. This system probes the changes in the hygroscopic properties of nanoparticles as volatile organic components are progressively evaporated. It also allows particle composition to be inferred from combined volatility-hygroscopicity measurements. Frequent new particle formation and growth events were observed during the Agnes Water campaign. The VH-TDMA was used to investigate freshly nucleated particles (17-22.5 nm) and it was found that the condensation of sulphate and/or organic vapours was responsible for driving particle growth during the events. Aitken mode particles (~40 nm) were also measured with the VH-TDMA. In 3 out of 18 VH-TDMA scans evaporation of a volatile, organic component caused a very large increase in hygroscopicity that could only be explained by an increase in the absolute water uptake of the particle residuals, and not merely an increase in their relative hygroscopicity. This indicated the presence of organic components that were suppressing the hygroscopic growth of mixed particles on the timescale of humidification in the VH-TDMA (6.5 secs). It was suggested that the suppression of water uptake was caused by either a reduced rate of hygroscopic growth due to the presence of organic films, or organic-inorganic interactions in solution droplets that had a negative effect on hygroscopicity. Mixed organic-inorganic particles were rarely observed by the VH-TDMA during the summer campaign conducted at Mace Head. The majority of particles below 100 nm in clean, marine air appeared to be sulphates neutralised to varying degrees by ammonia. On one unique day, 26 June 2007, particularly large concentrations of sulphate aerosol were observed and identified as volcanic emissions from Iceland. The degree of neutralisation of the sulphate aerosol by ammonia was calculated by the VH-TDMA and found to compare well with the same quantity measured by an aerosol mass spectrometer. This was an important verification of the VH-TMDA‘s ability to identify ammoniated sulphate aerosols based on the simultaneous measurement of aerosol volatility and hygroscopicity. A series of measurements were also conducted on sea spray aerosols generated from Moreton Bay seawater samples in a laboratory-based bubble chamber. Accumulation mode sea spray particles (38-173 nm) were found to contain only a minor organic fraction (< 10%) that had little effect on particle hygroscopicity. These results are important because previous studies have observed that accumulation mode sea spray particles are predominantly organic (~80% organic mass fraction). The work presented here suggests that this is not always the case, and that there may be currently unknown factors that are controlling the transfer of organics to the aerosol phase during the bubble bursting process. Taken together, the results of this research program have significantly improved our understanding of organic-containing marine aerosols and the way they interact with water vapour in the atmosphere.

“A problem of versions” : laying down the law in the school playground

Purpose This chapter investigates an episode where a supervising teacher on playground duty asks two boys to each give an account of their actions over an incident that had just occurred on some climbing equipment in the playground. Methodology This paper employs an ethnomethodological approach using conversation analysis. The data are taken from a corpus of video recorded interactions of children, aged 7-9 years, and the teacher, in school playgrounds during the lunch recess. Findings The findings show the ways that children work up accounts of their playground practices when asked by the teacher. The teacher initially provided interactional space for each child to give their version of the events. Ultimately, the teacher’s version of how to act in the playground became the sanctioned one. The children and the teacher formulated particular social orders of behavior in the playground through multi-modal devices, direct reported speech and scripts. Such public displays of talk work as socialization practices that frame teacher-sanctioned morally appropriate actions in the playground. Value of paper This chapter shows the pervasiveness of the teacher’s social order, as she presented an institutional social order of how to interact in the playground, showing clearly the disjunction of adult-child orders between the teacher and children.

Disputes in Everyday Life : Social and Moral Orders of Children and Young People

"The research presented in this volume has been undertaken in a range of settings and across ages, to display the rich, varied, and complex aspects of children and young people's everyday lives. The papers contribute to understanding children's disputes, framed as forms of social practice, by closely examining children's talk and interaction in disputes to offer insight into how they arrange their social lives within the context of school, home, neighborhood, correctional, and cafe settings. As such, this volume contributes to an emerging body of edited volumes that investigate children and young people's everyday interactions (Cromdal, 2009; Cromdal & Tholander, in press; Gardner & Forrester, 2010; Goodwin & Kyratzis, 2007; Hutchby & Moran-Ellis, 1998). Each paper has been peer reviewed, by respected researchers of the field, in some cases authors of this volume, and revised. We also thank Charlotte Cobb-Moore who so ably assisted in the final preparation of the manuscripts."---publisher website