Frequent activating FGFR2 mutations in endometrial carcinomas parallel germline mutations associated with craniosynostosis and skeletal dysplasia syndromes

Endometrial carcinoma is the most common gynecological malignancy in the United States. Although most women present with early disease confined to the uterus, the majority of persistent or recurrent tumors are refractory to current chemotherapies. We have identified a total of 11 different FGFR2 mutations in 3/10 (30%) of endometrial cell lines and 19/187 (10%) of primary uterine tumors. Mutations were seen primarily in tumors of the endometrioid histologic subtype (18/115 cases investigated, 16%). The majority of the somatic mutations identified were identical to germline activating mutations in FGFR2 and FGFR3 that cause Apert Syndrome, Beare-Stevenson Syndrome, hypochondroplasia, achondroplasia and SADDAN syndrome. The two most common somatic mutations identified were S252W (in eight tumors) and N550K (in five samples). Four novel mutations were identified, three of which are also likely to result in receptor gain-of-function. Extensive functional analyses have already been performed on many of these mutations, demonstrating they result in receptor activation through a variety of mechanisms. The discovery of activating FGFR2 mutations in endometrial carcinoma raises the possibility of employing anti-FGFR molecularly targeted therapies in patients with advanced or recurrent endometrial carcinoma.

Purification and characterization of heparan sulfate from human primary osteoblasts

Heparan sulfate (HS) is a linear, highly variable, highly sulfated glycosaminoglycan sugar whose biological activity largely depends on internal sulfated domains that mediate specific binding to an extensive range of proteins. In this study we employed anion exchange chromatography, molecular sieving and enzymatic cleavage on HS fractions purified from three compartments of cultured osteoblasts-soluble conditioned media, cell surface, and extracellular matrix (ECM). We demonstrate that the composition of HS chains purified from the different compartments is structurally non-identical by a number of parameters, and that these differences have significant ramifications for their ligand-binding properties. The HS chains purified of conditioned medium had twice the binding affinity for FGF2 when compared with either cell surface or ECM HS. In contrast, similar binding of BMP2 to the three types of HS was observed. These results suggest that different biological compartments of cultured cells have structurally and functionally distinct HS species that help to modulate the flow of HS-dependent factors between the ECM and the cell surface.

Predicting residue-wise contact orders in proteins by support vector regression

Background The residue-wise contact order (RWCO) describes the sequence separations between the residues of interest and its contacting residues in a protein sequence. It is a new kind of one-dimensional protein structure that represents the extent of long-range contacts and is considered as a generalization of contact order. Together with secondary structure, accessible surface area, the B factor, and contact number, RWCO provides comprehensive and indispensable important information to reconstructing the protein three-dimensional structure from a set of one-dimensional structural properties. Accurately predicting RWCO values could have many important applications in protein three-dimensional structure prediction and protein folding rate prediction, and give deep insights into protein sequence-structure relationships. Results We developed a novel approach to predict residue-wise contact order values in proteins based on support vector regression (SVR), starting from primary amino acid sequences. We explored seven different sequence encoding schemes to examine their effects on the prediction performance, including local sequence in the form of PSI-BLAST profiles, local sequence plus amino acid composition, local sequence plus molecular weight, local sequence plus secondary structure predicted by PSIPRED, local sequence plus molecular weight and amino acid composition, local sequence plus molecular weight and predicted secondary structure, and local sequence plus molecular weight, amino acid composition and predicted secondary structure. When using local sequences with multiple sequence alignments in the form of PSI-BLAST profiles, we could predict the RWCO distribution with a Pearson correlation coefficient (CC) between the predicted and observed RWCO values of 0.55, and root mean square error (RMSE) of 0.82, based on a well-defined dataset with 680 protein sequences. Moreover, by incorporating global features such as molecular weight and amino acid composition we could further improve the prediction performance with the CC to 0.57 and an RMSE of 0.79. In addition, combining the predicted secondary structure by PSIPRED was found to significantly improve the prediction performance and could yield the best prediction accuracy with a CC of 0.60 and RMSE of 0.78, which provided at least comparable performance compared with the other existing methods. Conclusion The SVR method shows a prediction performance competitive with or at least comparable to the previously developed linear regression-based methods for predicting RWCO values. In contrast to support vector classification (SVC), SVR is very good at estimating the raw value profiles of the samples. The successful application of the SVR approach in this study reinforces the fact that support vector regression is a powerful tool in extracting the protein sequence-structure relationship and in estimating the protein structural profiles from amino acid sequences.

FGFR2 mutations are rare across histologic subtypes of ovarian cancer

OBJECTIVE: Ovarian cancer is the leading cause of death from gynecologic malignancies in the Western world. Fibroblast growth factor receptor (FGFR) signaling has been implicated to play a role in ovarian tumorigenesis. Mutational activation of one member of this receptor family, FGFR2, is a frequent event in endometrioid endometrial cancer. Given the similarities in the histologic and molecular genetics of ovarian and endometrial cancers, we hypothesized that activating FGFR2 mutations may occur in a subset of endometrioid ovarian tumors, and possibly other histotypes. METHODS: Six FGFR2 exons were sequenced in 120 primary ovarian tumors representing the major histologic subtypes. RESULTS: FGFR2 mutation was detected at low frequency in endometrioid (1/46, 2.2%) and serous (1/41, 2.4%) ovarian cancer. No mutations were detected in clear cell, mucinous, or mixed histology tumors or in the ovarian cancer cell lines tested. Functional characterization of the FGFR2 mutations confirmed that the mutations detected in ovarian cancer result in receptor activation. CONCLUSIONS: Despite the low incidence of FGFR2 mutations in ovarian cancer, the two FGFR2 mutations identified in ovarian tumors (S252W, Y376C) overlap with the oncogenic mutations previously identified in endometrial tumors, suggesting activated FGFR2 may contribute to ovarian cancer pathogenesis in a small subset of ovarian tumors.

Rural and Urban Differentials in Primary Care Management of Chronic Heart Failure: New Data from the CASE Study

Objective: To determine whether primary care management of chronic heart failure (CHF) differed between rural and urban areas in Australia. Design: A cross-sectional survey stratified by Rural, Remote and Metropolitan Areas (RRMA) classification. The primary source of data was the Cardiac Awareness Survey and Evaluation (CASE) study. Setting: Secondary analysis of data obtained from 341 Australian general practitioners and 23 845 adults aged 60 years or more in 1998. Main outcome measures: CHF determined by criteria recommended by the World Health Organization, diagnostic practices, use of pharmacotherapy, and CHF-related hospital admissions in the 12 months before the study. Results: There was a significantly higher prevalence of CHF among general practice patients in large and small rural towns (16.1%) compared with capital city and metropolitan areas (12.4%) (P < 0.001). Echocardiography was used less often for diagnosis in rural towns compared with metropolitan areas (52.0% v 67.3%, P < 0.001). Rates of specialist referral were also significantly lower in rural towns than in metropolitan areas (59.1% v 69.6%, P < 0.001), as were prescribing rates of angiotensin-converting enzyme inhibitors (51.4% v 60.1%, P < 0.001). There was no geographical variation in prescribing rates of β-blockers (12.6% [rural] v 11.8% [metropolitan], P = 0.32). Overall, few survey participants received recommended “evidence-based practice” diagnosis and management for CHF (metropolitan, 4.6%; rural, 3.9%; and remote areas, 3.7%). Conclusions: This study found a higher prevalence of CHF, and significantly lower use of recommended diagnostic methods and pharmacological treatment among patients in rural areas.

Implementing dance in a Queensland primary school : a descriptive case study

This research documents and analyses the modes of implementation of the Dance component of The Arts Essential Learnings in a Queensland school. The research identifies what makes good practice in dance education and the multiple modes of implementation that support this practice. The primary purpose of this research is to describe the factors that influence dance education, as it is delivered, in a Queensland primary school to inform the development of further support for primary teachers and to improve the quality of dance education in Prep -7 schooling. The literature review investigates dance education both in Queensland, Australia and internationally, identifying current issues related to the delivery of dance in a primary school environment including barriers to implementation of dance, authentic learning and integrated approaches to learning. Based on Engestrom.s reformulation of Vygotsky.s theory of socially mediated learning, the implementation of dance education curriculum was explored through descriptive case study method. The case study was conducted in a regional Queensland school identified as delivering the dance curriculum in a variety of ways. The research project provided opportunities to observe, document and analyse how teachers deal with pedagogical dilemmas and solve logistical problems associated with teaching the dance component of the Arts curriculum in this school. Teachers. practices were contextualised through investigation of the whole school context of dance curriculum development. The findings revealed a range of teaching approaches that influenced teachers. interpretation and children.s experience of the dance curriculum. The features of a supportive whole school and cultural environment for dance were identified. These have been captured in a reworked version of Engestrom.s Second Generation Activity Theory that can be applied to the implementation of dance education in primary schools.

Crisis communication under transformative change : the emergent context and roles of primary and secondary organisations

In an era of complex challenges that draw sustained media attention and entangle multiple organisational actors, this thesis addresses the gap between current trends in society and business, and existing scholarship in public relations and crisis communication. By responding to calls from crisis communication researchers to develop theory (Coombs, 2006a), to examine the interdependencies of crises (Seeger, Sellnow, & Ulmer, 1998), and to consider variation in crisis response (Seeger, 2002), this thesis contributes to theory development in crisis communication and public relations. Through transformative change, this thesis extends existing scholarship built on a preservation or conservation logic where public relations is used to maintain stability by incrementally responding to changes in an organisation‘s environment (Cutlip, Center, & Broom, 2006; Everett, 2001; Grunig, 2000; Spicer, 1997). Based on the opportunity to contribute to ongoing theoretical development in the literature, the overall research problem guiding this thesis asks: How does transformative change during crisis influence corporate actors’ communication? This thesis adopts punctuated equilibrium theory, which describes change as alternating between long periods of stability and short periods of revolutionary or transformative change (Gersick, 1991; Romanelli & Tushman, 1994; Siggelkow, 2002; Tushman, Newman, & Romanelli, 1986; Tushman & Romanelli, 1985). As a theory for change, punctuated equilibrium provides an opportunity to examine public relations and transformative change, building on scholarship that is based primarily on incremental change. Further, existing scholarship in public relations and crisis communication focuses on the actions of single organisations in situational or short-term crisis events. Punctuated equilibrium theory enables the study of multiple crises and multiple organisational responses during transformative change. In doing so, punctuated equilibrium theory provides a framework to explain both the context for transformative change and actions or strategies enacted by organisations during transformative change (Tushman, Newman, & Romanelli, 1986; Tushman & Romanelli, 1985; Tushman, Virany, & Romanelli, 1986). The connections between context and action inform the research questions that guide this thesis: RQ1: What symbolic and substantive strategies persist and change as crises develop from situational events to transformative and multiple linked events? RQ2: What features of the crisis context influence changes in symbolic and substantive strategies? To shed light on these research questions, the thesis adopts a qualitative approach guided by process theory and methods to explicate the events, sequences and activities that were essential to change (Pettigrew, 1992; Van de Ven, 1992). Specifically, the thesis draws on an alternative template strategy (Langley, 1999) that provides several alternative interpretations of the same events (Allison, 1971; Allison & Zelikow, 1999). Following Allison (1971) and Allison and Zelikow (1999), this thesis uses three alternative templates of crisis or strategic response typologies to construct three narratives using media articles and organisational documents. The narratives are compared to identify and draw out different patterns of crisis communication strategies that operate within different crisis contexts. The thesis is based on the crisis events that affected three organisations within the pharmaceutical industry for four years. The primary organisation is Merck, as its product recall crisis triggered transformative change affecting, in different ways, the secondary organisations of Pfizer and Novartis. Three narratives are presented based on the crisis or strategic response typologies of Coombs (2006b), Allen and Caillouet (1994), and Oliver (1991). The findings of this thesis reveal different stories about crisis communication under transformative change. By zooming in to a micro perspective (Nicolini, 2009) to focus on the crisis communication and actions of a single organisation and zooming out to a macro perspective (Nicolini, 2009) to consider multiple organisations, new insights about crisis communication, change and the relationships among multiple organisations are revealed at context and action levels. At the context level, each subsequent narrative demonstrates greater connections among multiple corporate actors. By zooming out from Coombs‘ (2006b) focus on single organisations to consider Allen and Caillouet‘s (1994) integration of the web of corporate actors, the thesis demonstrates how corporate actors add accountability pressures to the primary organisation. Next, by zooming further out to the macro perspective by considering Oliver‘s (1991) strategic responses to institutional processes, the thesis reveals a greater range of corporate actors that are caught up in the process of transformative change and accounts for their varying levels of agency over their environment. By zooming in to a micro perspective and out to a macro perspective (Nicolini, 2009) across alternative templates, the thesis sheds light on sequences, events, and actions of primary and secondary organisations. Although the primary organisation remains the focus of sustained media attention across the four-year time frame, the secondary organisations, even when one faced a similar starting situation to the primary organisation, were buffered by the process of transformative change. This understanding of crisis contexts in transforming environments builds on existing knowledge in crisis communication. At the action level, the thesis also reveals different interpretations from each alternative template. Coombs‘ (2006b) narrative shows persistence in the primary organisation‘s crisis or strategic responses over the four-year time frame of the thesis. That is, the primary organisation consistently applies a diminish crisis response. At times, the primary organisation drew on denial responses when corporate actors questioned its legitimacy or actions. To close the crisis, the primary organisation uses a rebuild crisis posture (Coombs, 2006). These finding are replicated in Allen and Caillouet‘s (1994) narrative, noting this template‘s limitation to communication messages only. Oliver‘s (1991) narrative is consistent with Coombs‘ (2006b) but also demonstrated a shift from a strategic response that signals conformity to the environment to one that signals more active resistance to the environment over time. Specifically, the primary organisation‘s initial response demonstrates conformity but these same messages were used some three years later to set new expectations in the environment in order to shape criteria and build acceptance for future organisational decisions. In summary, the findings demonstrate the power of crisis or strategic responses when considered over time and in the context of transformative change. The conclusions of this research contribute to scholarship in the public relations and management literatures. Based on the significance of organisational theory, the primary contribution of the theory relates to the role of interorganisational linkages or legitimacy buffers that form during the punctuation of equilibrium. The network of linkages among the corporate actors are significant also to the crisis communication literature as they form part of the process model of crisis communication under punctuated equilibrium. This model extends existing research that focuses on crisis communication of single organisations to consider the emergent context that incorporates secondary organisations as well as the localised contests of legitimacy and buffers from regulatory authorities. The thesis also provides an empirical base for punctuated equilibrium in public relations and crisis communication, extending Murphy‘s (2000) introduction of the theory to the public relations literature. In doing this, punctuated equilibrium theory reinvigorates theoretical development in crisis communication by extending existing scholarship around incrementalist approaches and demonstrating how public relations works in the context of transformative change. Further research in this area could consider using alternative templates to study transformative change caused by a range of crisis types from natural disasters to product tampering, and to add further insight into the dynamics between primary and secondary organisations. This thesis contributes to practice by providing guidelines for crisis response strategy selection and indicators related to the emergent context for crises under transformative change that will help primary and secondary organisations‘ responses to crises.

A case study of how primary school teachers in Papua New Guinea understand outcomes-based education

This case study explored how a group of primary school teachers in Papua New Guinea (PNG) understood Outcomes-based Education (OBE). OBE measures students. learning against specific outcomes. These outcomes are derived from a country.s vision of the kind of citizen that the education system should produce. While countries such as Australia, South Africa, New Zealand and the United States have abandoned OBE, others such as PNG have adopted it in various ways. How teachers understand OBE in PNG is important because such understandings are likely to influence how they implement the OBE curriculum. There has been no research to date which has investigated PNG primary school teachers. understandings and experiences with OBE. This study used a single exploratory case study design to investigate how twenty primary school teachers from the National Capital District (NCD) in PNG understood OBE. The study, underpinned by an intepretivist paradigm, explored the research question: How do primary school teachers understand outcomes-based education in PNG? The data comprised surveys, in-depth interviews and documents. Data were analysed thematically and using explanation building techniques. The findings revealed that OBE is viewed by teachers as a way to equip them with additional strategies for planning and programming, teaching and learning, and assessment. Teachers also described how OBE enabled both students and teachers to become more engaged and develop positive attitudes towards teaching and learning. There was also a perception that OBE enhanced students. future life skills through increased local community support. While some teachers commented on how the OBE reforms provided them with increased professional development opportunities, the greatest impediment to implementing OBE was perceived to be a lack of sufficient teaching and learning resources. The process of planning and programming classroom activities was also regarded as onerous. Some teachers indicated that they had been required to implement OBE without adequate in-service training support. The social constructivist theory of knowledge which underpins OBE.s student-centred pedagogy can cause tensions within PNG.s cultural contexts of teaching and learning. Teachers need to be aware of these tensions when conducting peer or group learning under OBE in PNG. By exploring how these PNG primary teachers understood OBE, the study highlighted how teachers engaged with OBE concepts when interpreting syllabus documents and how they applied these concepts to curriculum. Identifying differences in teacher understanding of OBE provides guidance for both the design of materials to support the implementation of OBE and for the design of in-service training. Thus, the outcomes of this study will inform educators about the implementation of OBE in PNG. In addition, the outcomes will provide much needed insight into how a mandated curriculum and pedagogical reform impacts teachers‟ practices in PNG.

Library and information science education 2.0: guiding principles and models of best practice. Interview with Sue Reynolds.

In 2005, Stephen Abram, vice president of Innovation at SirsiDynix, challenged library and information science (LIS) professionals to start becoming “librarian 2.0.” In the last few years, discussion and debate about the “core competencies” needed by librarian 2.0 have appeared in the “biblioblogosphere” (blogs written by LIS professionals). However, beyond these informal blog discussions few systematic and empirically based studies have taken place. A project funded by the Australian Learning and Teaching Council fills this gap. The project identifies the key skills, knowledge, and attributes required by “librarian 2.0.” Eighty-one members of the Australian LIS profession participated in a series of focus groups. Eight themes emerged as being critical to “librarian 2.0”: technology, communication, teamwork, user focus, business savvy, evidence based practice, learning and education, and personal traits. Guided by these findings interviews with 36 LIS educators explored the current approaches used within contemporary LIS education to prepare graduates to become “librarian 2.0”. This video presents an example of ‘great practice’ in current LIS educative practice in helping to foster web 2.0 professionals.

Library and information science education 2.0 : guiding principles and models of best practice : interview with John Terrell

In 2005, Stephen Abram, vice president of Innovation at SirsiDynix, challenged library and information science (LIS) professionals to start becoming “librarian 2.0.” In the last few years, discussion and debate about the “core competencies” needed by librarian 2.0 have appeared in the “biblioblogosphere” (blogs written by LIS professionals). However, beyond these informal blog discussions few systematic and empirically based studies have taken place. A project funded by the Australian Learning and Teaching Council fills this gap. The project identifies the key skills, knowledge, and attributes required by “librarian 2.0.” Eighty-one members of the Australian LIS profession participated in a series of focus groups. Eight themes emerged as being critical to “librarian 2.0”: technology, communication, teamwork, user focus, business savvy, evidence based practice, learning and education, and personal traits. Guided by these findings interviews with 36 LIS educators explored the current approaches used within contemporary LIS education to prepare graduates to become “librarian 2.0”. This video presents an example of ‘great practice’ in current LIS education as it strives to foster web 2.0 professionals.

Library and information science education 2.0 : guiding principles and models of best practice : interview with Kate Davis.

In 2005, Stephen Abram, vice president of Innovation at SirsiDynix, challenged library and information science (LIS) professionals to start becoming “librarian 2.0.” In the last few years, discussion and debate about the “core competencies” needed by librarian 2.0 have appeared in the “biblioblogosphere” (blogs written by LIS professionals). However, beyond these informal blog discussions few systematic and empirically based studies have taken place. A project funded by the Australian Learning and Teaching Council fills this gap. The project identifies the key skills, knowledge, and attributes required by “librarian 2.0.” Eighty-one members of the Australian LIS profession participated in a series of focus groups. Eight themes emerged as being critical to “librarian 2.0”: technology, communication, teamwork, user focus, business savvy, evidence based practice, learning and education, and personal traits. Guided by these findings interviews with 36 LIS educators explored the current approaches used within contemporary LIS education to prepare graduates to become “librarian 2.0”. This video presents an example of ‘great practice’ in current LIS education as it strives to foster web 2.0 professionals.

Scaffolding techniques : a teacher training for cooperative learning in Thailand primary education

In general, the benefits of using cooperative learning include academic achievement, communication skills, problem-solving, social skills and student motivation. Yet cooperative learning as a Western educational concept may be ineffective in a different learning system. The study aims to investigate scaffolding techniques for cooperative learning in Thailand primary education. The program was designed to foster Thai primary school teachers’ cooperative learning implementation that includes the basic tenets of cooperative learning and socio-cognitive based learning. Two teachers were invited to participate in this experimental teacher training program for one and a half weeks. Then the teachers implemented a cooperative learning in their mathematics class for six weeks. The data from teacher interview and classroom observation indicated that the both teachers are able to utilise questions to scaffold their students’ engagement in cooperative learning. This initiative study showed that difficulty or failure of implementing cooperative learning in Thailand education may not be derived from cultural difference. The paper discussed the techniques the participant teachers applied with proactive scaffolding, reactive scaffolding and scaffolding questions that can be used to facilitate the implementation of cooperative learning in Thai school.