Phase I trial of the combination of the Akt inhibitor nelfinavir and chemoradiation for locally advanced rectal cancer

PURPOSE: To investigate the toxicity of nelfinavir, administered during preoperative chemoradiotherapy (CRT) in patients with locally advanced cancer. MATERIAL AND METHODS: Twelve patients were treated with to 50.4Gy combined with capecitabine 825mg/m2 BID. Three dose levels nelfinavir were tested: 750mg BID (DL1), 1250mg BID (DL2) and an level of 1000mg BID (DL3). Surgery was performed between 8 and 10weeks completion of CRT. Primary endpoint was dose-limiting toxicity (DLT), any grade 3 or higher non-hematological or grade 4 or higher toxicity. RESULTS: Eleven patients could be analyzed: 5 were treated in DL2 and 3 in DL3. The first 3 patients in DL1 did not develop a DLT. In patient developed gr 3 diarrhea, 1 patient had gr 3 transaminase patient had a gr 3 cholangitis with unknown cause. An intermediate dose tested in DL3. In this group 2 patients developed gr 3 diarrhea and 1 3 transaminase elevation and gr 4 post-operative wound complication. patients achieved a pathological complete response (pCR). CONCLUSIONS: 750mg BID was defined as the recommended phase II dose in combination capecitabine and 50.4Gy pre-operative radiotherapy in rectal cancer. response evaluations are promising, but a further phase II study is more information about efficacy of this treatment regimen

Accuracy of screening women at familial risk of breast cancer without a known gene mutation:individual patient data meta-analysis

Introduction Women with a strong family history of breast cancer (BC) and without a known gene mutation have an increased risk of developing BC. We aimed to investigate the accuracy of screening using annual mammography with or without magnetic resonance imaging (MRI) for these women outside the general population screening program. Methods An individual patient data (IPD) meta-analysis was conducted using IPD from six prospective screening trials that had included women at increased risk for BC: only women with a strong familial risk for BC and without a known gene mutation were included in this analysis. A generalised linear mixed model was applied to estimate and compare screening accuracy (sensitivity, specificity and predictive values) for annual mammography with or without MRI. Results There were 2226 women (median age: 41 years, interquartile range 35–47) with 7478 woman-years of follow-up, with a BC rate of 12 (95% confidence interval 9.3–14) in 1000 woman-years. Mammography screening had a sensitivity of 55% (standard error of mean [SE] 7.0) and a specificity of 94% (SE 1.3). Screening with MRI alone had a sensitivity of 89% (SE 4.6) and a specificity of 83% (SE 2.8). Adding MRI to mammography increased sensitivity to 98% (SE 1.8, P &lt; 0.01 compared to mammography alone) but lowered specificity to 79% (SE 2.7, P &lt; 0.01 compared with mammography alone). Conclusion In this population of women with strong familial BC risk but without a known gene mutation, in whom BC incidence was high both before and after age 50, adding MRI to mammography substantially increased screening sensitivity but also decreased its specificity.</p

Designing for interaction immediacy to enhance social skills of children with autism

Children with Autism Spectrum Disorder often require therapeutic interventions to support engagement in effective social interactions. In this paper, we present the results of a study conducted in three public schools that use an educational and behavioral intervention for the instruction of social skills in changing situational contexts. The results of this study led to the concept of interaction immediacy to help children maintain appropriate spatial boundaries, reply to conversation initiators, disengage appropriately at the end of an interaction, and identify potential communication partners. We describe design principles for Ubicomp technologies to support interaction immediacy and present an example design. The contribution of this work is twofold. First, we present an understanding of social skills in mobile and dynamic contexts. Second, we introduce the concept of interaction immediacy and show its effectiveness as a guiding principle for the design of Ubicomp applications

Story Generation in PDDL Using Character Moods: A Case Study on Iliad's First Book

In this paper we look into a simple approach for generating character-based stories using planning and the language of PDDL. A story often involves modalities over properties and objects, such as what the characters believe, desire, request, etc. We look into a practical approach that reifies such modalities into normal objects of the planning domain, and relies on a "mood" predicate to represent the disposition of characters based on these objects. A short story is then generated by specifying a goal for the planning problem expressed in terms of the moods of the characters of the story. As a case study of how such a domain for story generation is modeled, we investigate the story of the first book of Homer's Iliad as a solution of an appropriate PDDL domain and problem description