Sentence planning and production in Murrinhpatha, an Australian 'free word order' language

Psycholinguistic theories are based on a very small set of unrepresentative languages, so it is as yet unclear how typological variation shapes mechanisms supporting language use. In this article we report the first on-line experimental study of sentence production in an Australian free word order language: Murrinhpatha. Forty-six adult native speakers of Murrinhpatha described a series of unrelated transitive scenes that were manipulated for humanness (±human) in the agent and patient roles while their eye movements were recorded. Speakers produced a large range of word orders, consistent with the language having flexible word order, with variation significantly influenced by agent and patient humanness. An analysis of eye movements showed that Murrinhpatha speakers' first fixation on an event character did not alone determine word order; rather, early in speech planning participants rapidly encoded both event characters and their relationship to each other. That is, they engaged in relational encoding, laying down a very early conceptual foundation for the word order they eventually produced. These results support a weakly hierarchical account of sentence production and show that speakers of a free word order language encode the relationships between event participants during earlier stages of sentence planning than is typically observed for languages with fixed word orders

Prosodic phrasing, pitch range, and word order variation in Murrinhpatha

Like many Indigenous Australian languages, Murrinhpatha has flexible word order with no apparent configurational syntax. We analyzed an experimental corpus of Murrinhpatha utterances for associations between different thematic role orders, intonational phrasing patterns and pitch downtrends. We found that initial constituents (Agents or Patients) tend to carry the highest pitch targets (HiF0), followed by patterns of downstep and declination. Sentence-final verbs always have lower Hif0 values than either initial or medial Agents or Patients. Thematic role order does not influence intonational patterns, with the results suggesting that Murrinhpatha has positional prosody, although final nominals can disrupt global pitch downtrends regardless of thematic role

Phase II study of helical tomotherapy in the multidisciplinary treatment of oligometastatic colorectal cancer

<p>Abstract</p> <p>Background</p> <p>Complete metastasectomy provides a real chance for long-term survival in patients with oligometastatic colorectal cancer (CRC). For inoperable patients, we evaluated in this study intensity-modulated and image-guided radiotherapy (IMRT-IGRT) by helical tomotherapy.</p> <p>Methods</p> <p>Twenty-four CRC patients with ≤ 5 metastases were enrolled, receiving a dose of 50 Gy in fractions of 5 Gy. No limitations concerning dimension or localization of the metastases were imposed. Whole body PET-CT was performed at baseline and 3 months after the initiation of RT to evaluate the metabolic response rate according to PET Response Criteria in Solid Tumors (PERCIST) version 1.0.</p> <p>Results</p> <p>A total of 53 metastases were treated. Seventeen patients (71%) received previously ≥ 1 line of chemotherapy for metastatic disease, displaying residual (n = 7) or progressive (n = 10) metabolic active oligometastatic disease at time of inclusion. Most common sites were the lung, liver and lymphnodes. One patient (4%) experienced grade 3 dysphagia. Twenty-two patients were evaluated by post-treatment PET-CT. Twelve patients achieved a complete (n = 6) or partial (n = 6) metabolic response, resulting in an overall metabolic response rate of 55%. At a median follow-up of 10 months, 7 patients (29%) are in remission, of which 5 received previous chemotherapy with residual oligometastatic disease at time of inclusion. The actuarial 1-year local control, progression-free survival, and overall survival were 54%, 14% and 78%.</p> <p>Conclusions</p> <p>Helical tomotherapy delivering 10 fractions of 5 Gy resulted in a metabolic response rate of 55%, and appeared to be attractive as consolidation of inoperable oligometastatic disease after effective chemotherapy.</p> <p>Trial registration</p> <p>Eudract 2008-008300-40; <a href="http://www.clinicaltrials.gov/ct2/show/NCT00807313">NCT00807313</a></p

Matrix-comparative genomic hybridization from multicenter formalin-fixed paraffin-embedded colorectal cancer tissue blocks

<p>Abstract</p> <p>Background</p> <p>The identification of genomic signatures of colorectal cancer for risk stratification requires the study of large series of cancer patients with an extensive clinical follow-up. Multicentric clinical studies represent an ideal source of well documented archived material for this type of analyses.</p> <p>Methods</p> <p>To verify if this material is technically suitable to perform matrix-CGH, we performed a pilot study using macrodissected 29 formalin-fixed, paraffin-embedded tissue samples collected within the framework of the EORTC-GI/PETACC-2 trial for colorectal cancer. The scientific aim was to identify prognostic genomic signatures differentiating locally restricted (UICC stages II-III) from systemically advanced (UICC stage IV) colorectal tumours.</p> <p>Results</p> <p>The majority of archived tissue samples collected in the different centers was suitable to perform matrix-CGH. 5/7 advanced tumours displayed 13q-gain and 18q-loss. In locally restricted tumours, only 6/12 tumours showed a gain on 13q and 7/12 tumours showed a loss on 18q. Interphase-FISH and high-resolution array-mapping of the gain on 13q confirmed the validity of the array-data and narrowed the chromosomal interval containing potential oncogenes.</p> <p>Conclusion</p> <p>Archival, paraffin-embedded tissue samples collected in multicentric clinical trials are suitable for matrix-CGH analyses and allow the identification of prognostic signatures and aberrations harbouring potential new oncogenes.</p

Neoadjuvant FOLFIRI+bevacizumab in patients with resectable liver metastases from colorectal cancer: a phase 2 trial.

BACKGROUND: Preoperative treatment of resectable liver metastases from colorectal cancer (CRC) is a matter of debate. The aim of this study was to assess the feasibility and activity of bevacizumab plus FOLFIRI in this setting. METHODS: Patients aged 18-75 years, PS 0-1, with resectable liver-confined metastases from CRC were eligible. They received bevacizumab 5 mg kg(-1) followed by irinotecan 180 mg m(-)(2), leucovorin 200 mg m(-)(2), 5-fluorouracil 400 mg m(-)(2) bolus and 5-fluorouracil 2400 mg m(-)(2) 46-h infusion, biweekly, for 7 cycles. Bevacizumab was stopped at cycle 6. A single-stage, single-arm phase 2 study design was applied with 1-year progression-free rate as the primary end point, and 39 patients required. RESULTS: From October 2007 to December 2009, 39 patients were enrolled in a single institution. Objective response rate was 66.7% (95% exact CI: 49.8-80.9). Of these, 37 patients (94.9%) underwent surgery, with a R0 rate of 84.6%. Five patients had a pathological complete remission (14%). Out of 37 patients, 16 (43.2%) had at least one surgical complication (most frequently biloma). At 1 year of follow-up, 24 patients were alive and free from disease progression (61.6%, 95% CI: 44.6-76.6). Median PFS and OS were 14 (95% CI: 11-24) and 38 (95% CI: 28-NA) months, respectively. CONCLUSION: Preoperative treatment of patients with resectable liver metastases from CRC with bevacizumab plus FOLFIRI is feasible, but further studies are needed to define its clinical relevance

The management of pancreatic cancer. Current expert opinion and recommendations derived from the 8th World Congress on Gastrointestinal Cancer, Barcelona, 2006

This article summarizes the expert discussion on the management of pancreatic cancer, which took place during the 8th World Congress on Gastrointestinal Cancer in June 2006 in Barcelona. A multidisciplinary approach to a patient with pancreatic cancer is essential, in order to guarantee an optimal staging, surgery, selection of the appropriate (neo-)adjuvant strategy and chemotherapeutic choice management. Moreover, optimal symptomatic management requires a dedicated team of health care professionals. Quality control of surgery and pathology is especially important in this disease with a high locoregional failure rate. There is now solid evidence in favour of chemotherapy in both the adjuvant and palliative setting, and gemcitabine combined with erlotinib, capecitabine or platinum compounds seems to be slightly more active than gemcitabine alone in advanced pancreatic cancer. There is a place for chemoradiotherapy in selected patients with locally advanced disease, while the role in the adjuvant setting remains controversial. Those involved in the care for patients with pancreatic cancer should be encouraged to participate in well-designed clinical trials, in order to increase the evidence-based knowledge and to make further progres

Defining patient outcomes in stage IV colorectal cancer: a prospective study with baseline stratification according to disease resectability status

BACKGROUND: Stage IV colorectal cancer encompasses a broad patient population in which both curative and palliative management strategies may be used. In a phase II study primarily designed to assess the efficacy of capecitabine and oxaliplatin, we were able to prospectively examine the outcomes of patients with stage IV colorectal cancer according to the baseline resectability status. METHODS: At enrolment, patients were stratified into three subgroups according to the resectability of liver disease and treatment intent: palliative chemotherapy (subgroup A), conversion therapy (subgroup B) or neoadjuvant therapy (subgroup C). All patients received chemotherapy with capecitabine 2000 mg m(-2) on days 1-14 and oxaliplatin 130 mg m(-2) on day 1 repeated every 3 weeks. Imaging was repeated every four cycles where feasible liver resection was undertaken after four or eight cycles of chemotherapy. RESULTS: Of 128 enrolled patients, 74, 22 and 32 were stratified into subgroups A, B and C, respectively. Attempt at curative liver resection was undertaken in 10 (45%) patients in subgroup B and 19 (59%) in subgroup C. The median overall survival was 14.6, 24.5 and 52.9 months in subgroups A, B and C, respectively. For patients in subgroups B and C who underwent an attempt at curative resection, 3-year progression-free survival was 10% in subgroup B and 37% for subgroup C. CONCLUSIONS: This prospective study shows the wide variation in outcome according to baseline resectability status and highlights the potential clinical value of a modified staging system to distinguish between these patient subgroups. British Journal of Cancer (2010) 102, 255-261. doi:10.1038/sj.bjc.6605508 www.bjcancer.com (C) 2010 Cancer Research U