FGFR2 point mutations in 466 Endometrioid Endometrial Tumors : relationship with MSI, KRAS, PIK3CA, CTNNB1 mutations and Clinicopathological features

Mutations in multiple oncogenes including KRAS, CTNNB1, PIK3CA and FGFR2 have been identified in endometrial cancer. The aim of this study was to provide insight into the clinicopathological features associated with patterns of mutation in these genes, a necessary step in planning targeted therapies for endometrial cancer. 466 endometrioid endometrial tumors were tested for mutations in FGFR2, KRAS, CTNNB1, and PIK3CA. The relationships between mutation status, tumor microsatellite instability (MSI) and clinicopathological features including overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan-Meier survival analysis and Cox proportional hazard models. Mutations were identified in FGFR2 (48/466); KRAS (87/464); CTNNB1 (88/454) and PIK3CA (104/464). KRAS and FGFR2 mutations were significantly more common, and CTNNB1 mutations less common, in MSI positive tumors. KRAS and FGFR2 occurred in a near mutually exclusive pattern (p = 0.05) and, surprisingly, mutations in KRAS and CTNNB1 also occurred in a near mutually exclusive pattern (p = 0.0002). Multivariate analysis revealed that mutation in KRAS and FGFR2 showed a trend (p = 0.06) towards longer and shorter DFS, respectively. In the 386 patients with early stage disease (stage I and II), FGFR2 mutation was significantly associated with shorter DFS (HR = 3.24; 95% confidence interval, CI, 1.35-7.77; p = 0.008) and OS (HR = 2.00; 95% CI 1.09-3.65; p = 0.025) and KRAS was associated with longer DFS (HR = 0.23; 95% CI 0.05-0.97; p = 0.045). In conclusion, although KRAS and FGFR2 mutations share similar activation of the MAPK pathway, our data suggest very different roles in tumor biology. This has implications for the implementation of anti-FGFR or anti-MEK biologic therapies.

Green Exercise in the UK Countryside: Effects on Health and Psychological Well-being and Implications for Policy and Planning

There is evidence that contact with the natural environment and green space promotes good health. It is also well known that participation in regular physical activity generates physical and psychological health benefits. The authors have hypothesised that ‘green exercise’ will improve health and psychological well-being, yet few studies have quantified these effects. This study measured the effects of 10 green exercise case studies (including walking, cycling, horse-riding, fishing, canal-boating and conservation activities) in four regions of the UK on 263 participants. Even though these participants were generally an active and healthy group, it was found that green exercise led to a significant improvement in self-esteem and total mood disturbance (with anger-hostility, confusion-bewilderment, depression-dejection and tension-anxiety all improving post-activity). Self-esteem and mood were found not to be affected by the type, intensity or duration of the green exercise, as the results were similar for all 10 case studies. Thus all these activities generated mental health benefits, indicating the potential for a wider health and well-being dividend from green exercise. Green exercise thus has important implications for public and environmental health, and for a wide range of policy sectors.

School Leadership, Literacy and Social Justice : The Place of Local School Curriculum Planning and Reform

School reform is a matter of both redistributive social justice and recognitive social justice. Following Fraser (Justice interruptus: critical reflections on the “postsocialist” condition. Routledge, New York, 1997), we begin from a philosophical and political commitment to the more equitable redistribution of knowledge, credentials, competence, and capacity to children of low socioeconomic, cultural, and linguistic minority and Indigenous communities whose access, achievement, and participation historically have “lagged” behind system norms and benchmarks set by middle class and dominant culture communities. At the same time, we argue that the recognition of these students and their communities’ lifeworlds, knowledges, and experiences in the curriculum, in classroom teaching, and learning is both a means and an end: a means toward improved achievement measured conventionally and a goal for reform and alteration of mainstream curriculum knowledge and what is made to count in the school as valued cultural knowledge and practice. The work that we report here was based on an ongoing 4-year project where a team of university teacher educators/researchers have partnered with school leadership and staff to build relationships within community. The purpose has been to study whether and how engagement with new digital arts and multimodal literacies could have effects on students “conventional” print literacy achievement and, secondly, to study whether and how the overall performance of a school could be generated through a focus on professional conversations and partnerships in curriculum and instruction – rather than the top-down implementation of a predetermined pedagogical scheme, package, or approach.

Persistence of multiple genetic lineages within intra-host populations of Ross River virus

We examined the structure and extent of genetic diversity in intrahost populations of Ross River virus (RRV) in samples from six human patients, focusing on the nonstructural (nsP3) and structural (E2) protein genes. Strikingly, although the samples were collected from contrasting ecological settings 3,000 kilometers apart in Australia, we observed multiple viral lineages in four of the six individuals, which is indicative of widespread mixed infections. In addition, a comparison with previously published RRV sequences revealed that these distinct lineages have been in circulation for at least 5 years, and we were able to document their long-term persistence over extensive geographical distances

A capability framework visualisation for multiple heterogeneous UAVs : from a mission commander's perspective

There is an increased interested in Uninhabited Aerial Vehicle (UAV) operations and research into advanced methods for commanding and controlling multiple heterogeneous UAVs. Research into areas of supervisory control has rapidly increased. Past research has investigated various approaches of autonomous control and operator limitation to improve mission commanders' Situation Awareness (SA) and cognitive workload. The aim of this paper is to address this challenge through a visualisation framework of UAV information constructed from Information Abstraction (IA). This paper presents the concept and process of IA, and the visualisation framework (constructed using IA), the concept associated with the Level Of Detail (LOD) indexing method, the visualisation of an example of the framework. Experiments will test the hypothesis that, the operator will be able to achieve increased SA and reduced cognitive load with the proposed framework.

The developmental consequences of rare chromosome disorders : two case reports

Aim: As molecular and cytogenetic testing becomes increasingly sophisticated, more individuals are being diagnosed with rare chromosome disorders. Yet despite a burgeoning knowledge about biomedical aspects, little is known about implications for psychosocial development. The scant literature gives a general impression of deficits and adverse developmental outcomes. Method: Developmental data were obtained from two 16 year olds diagnosed with a rare chromosome disorder – a girl with 8p23.1 and a boy with 16q11.2q12.1. Measures of intellectual ability, academic achievement, and other aspects of functioning were administered at multiple time points from early childhood to adolescence. Results: Both adolescents experienced initial delays in motor and language development. Although the girl’s intelligence is assessed as being in the average range, she experiences difficulties with motor planning, spelling and writing. The boy has been diagnosed with a mild intellectual disability and demonstrates mild autistic features. Conclusions: The two case descriptions are in marked contrast to the published literature about these two chromosome anomalies. Both adolescents are developing much more positively than would be expected on the basis of the grim predictions of their paediatricians and the negative reports in the literature. It is concluded that, for most rare chromosome disorders, the range of possible developmental outcomes is currently unknown.

Business planning in emerging firms : do nascent and young firms use business planning differently

Previous research suggested that due to the uncertainties surrounding the venture creation process, planning activities may be more valuable for already operating firms than for emerging ventures (McGrath and MacMillan, 1995). Business planning may serve different purposes during the early stages of the venture development process. Early planning during the nascent stage may be used to marshal the resources toward the achievement of preliminary goals (Locke and Latham, 2000), to gain external legitimization and funding (Karlssson & Honig, 2009; Stinchcombe, 1965). Planning may reduce the risk of future failure by facilitating the decision making process of launching -or not- the venture (Chwolka & Raith, 2011) by analysing the opportunity and its market potential (Boyd, 1991; Delmar & Shane, 2003). In later stages, planning may have a more internal role and may act as a strategic implementation tool (Brews & Hunt, 1999). However, if the reasons why ventures should engage (Frese, 2009) –or not- (Honig, 2004) in business planning have been investigated quite extensively (Brinckmann et al., 2010), how business plans are actually used over time by new ventures at different stages of their development and how these uses impact the performance of the firms are still unclear.

Multiple cameras for audio-visual speech recognition in an automotive environment

Audio-visualspeechrecognition, or the combination of visual lip-reading with traditional acoustic speechrecognition, has been previously shown to provide a considerable improvement over acoustic-only approaches in noisy environments, such as that present in an automotive cabin. The research presented in this paper will extend upon the established audio-visualspeechrecognition literature to show that further improvements in speechrecognition accuracy can be obtained when multiple frontal or near-frontal views of a speaker's face are available. A series of visualspeechrecognition experiments using a four-stream visual synchronous hidden Markov model (SHMM) are conducted on the four-camera AVICAR automotiveaudio-visualspeech database. We study the relative contribution between the side and central orientated cameras in improving visualspeechrecognition accuracy. Finally combination of the four visual streams with a single audio stream in a five-stream SHMM demonstrates a relative improvement of over 56% in word recognition accuracy when compared to the acoustic-only approach in the noisiest conditions of the AVICAR database.