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.

Robust designs for Poisson regression models

We consider the problem of how to construct robust designs for Poisson regression models. An analytical expression is derived for robust designs for first-order Poisson regression models where uncertainty exists in the prior parameter estimates. Given certain constraints in the methodology, it may be necessary to extend the robust designs for implementation in practical experiments. With these extensions, our methodology constructs designs which perform similarly, in terms of estimation, to current techniques, and offers the solution in a more timely manner. We further apply this analytic result to cases where uncertainty exists in the linear predictor. The application of this methodology to practical design problems such as screening experiments is explored. Given the minimal prior knowledge that is usually available when conducting such experiments, it is recommended to derive designs robust across a variety of systems. However, incorporating such uncertainty into the design process can be a computationally intense exercise. Hence, our analytic approach is explored as an alternative.

Continuous and pedagogically sound assessment : A new economy of power relations in Australian Law schools

In recent decades, assessment practices within Australian law schools have moved from the overwhelming use of end-of-year closed-book examinations to an increase in the use of a wider range of techniques. This shift is often characterised as providing a ‘better’ learning environment for students, contributing more positively to their own ‘personal development’ within higher education, or, considered along the lines of critical legal thought, as ‘liberating’ them from the ‘conservatising’ and ‘indoctrinating’ effects of the power relations that operate in law schools. This paper seeks to render problematic such liberal-progressive narratives about these changes to law school assessment practices. It will do so by utilising the work of French historian and philosopher Michel Foucault on power, arguing that the current range of assessment techniques demonstrates a shift in the ‘economy’ of power relations within the law school. Rather than ‘liberating’ students from relations of power, these practices actually extend the power relations through which students are governed. This analysis is intended to inform legal education research and assessment practice by providing a far more nuanced conceptual framework than one that seeks to ‘free’ law students from these ‘repressive’ practices, or hopes to ‘objectively’ contribute to their ‘personal development’.