29 research outputs found

    Testing statistical learning implicitly: A novel chunk-based measure of statistical learning

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    Attempts to connect individual differences in statistical learning with broader aspects of cognition have received considerable attention, but have yielded mixed results. A possible explanation is that statistical learning is typically tested using the two-alternative forced choice (2AFC) task. As a meta-cognitive task relying on explicit familiarity judgments, 2AFC may not accurately capture implicitly formed statistical computations. In this paper, we adapt the classic serial-recall memory paradigm to implicitly test statistical learning in a statistically-induced chunking recall (SICR) task. We hypothesized that artificial language exposure would lead subjects to chunk recurring statistical patterns, facilitating recall of words from the input. Experiment 1 demonstrates that SICR offers more fine-grained insights into individual differences in statistical learning than 2AFC. Experiment 2 shows that SICR has higher test-retest reliability than that reported for 2AFC. Thus, SICR offers a more sensitive measure of individual differences, suggesting that basic chunking abilities may explain statistical learning

    A combined ULBP2 and SEMA5A expression signature as a prognostic and predictive biomarker for colon cancer

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    Background: Prognostic biomarkers for cancer have the power to change the course of disease if they add value beyond known prognostic factors, if they can help shape treatment protocols, and if they are reliable. The aim of this study was to identify such biomarkers for colon cancer and to understand the molecular mechanisms leading to prognostic stratifications based on these biomarkers. Methods and Findings: We used an in house R based script (SSAT) for the in silico discovery of stage-independent prognostic biomarkers using two cohorts, GSE17536 and GSE17537, that include 177 and 55 colon cancer patients, respectively. This identified 2 genes, ULBP2 and SEMA5A, which when used jointly, could distinguish patients with distinct prognosis. We validated our findings using a third cohort of 48 patients ex vivo. We find that in all cohorts, a combined ULBP2/SEMA5A classification (SU-GIB) can stratify distinct prognostic sub-groups with hazard ratios that range from 2.4 to 4.5 (p=0.01) when overall- or cancer-specific survival is used as an end-measure, independent of confounding prognostic parameters. In addition, our preliminary analyses suggest SU-GIB is comparable to Oncotype DX colon(Ÿ) in predicting recurrence in two different cohorts (HR: 1.5-2; p=0.02). SU-GIB has potential as a companion diagnostic for several drugs including the PI3K/mTOR inhibitor BEZ235, which are suitable for the treatment of patients within the bad prognosis group. We show that tumors from patients with worse prognosis have low EGFR autophosphorylation rates, but high caspase 7 activity, and show upregulation of pro-inflammatory cytokines that relate to a relatively mesenchymal phenotype. Conclusions: We describe two novel genes that can be used to prognosticate colon cancer and suggest approaches by which such tumors can be treated. We also describe molecular characteristics of tumors stratified by the SU-GIB signature. © Ivyspring International Publisher

    Adjuvant Autologous Melanoma Vaccine for Macroscopic Stage III Disease: Survival, Biomarkers, and Improved Response to CTLA-4 Blockade

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    Background. There is not yet an agreed adjuvant treatment for melanoma patients with American Joint Committee on Cancer stages III B and C. We report administration of an autologous melanoma vaccine to prevent disease recurrence. Patients and Methods. 126 patients received eight doses of irradiated autologous melanoma cells conjugated to dinitrophenyl and mixed with BCG. Delayed type hypersensitivity (DTH) response to unmodified melanoma cells was determined on the vaccine days 5 and 8. Gene expression analysis was performed on 35 tumors from patients with good or poor survival. Results. Median overall survival was 88 months with a 5-year survival of 54%. Patients attaining a strong DTH response had a significantly better (p = 0.0001) 5-year overall survival of 75% compared with 44% in patients without a strong response. Gene expression array linked a 50-gene signature to prognosis, including a cluster of four cancer testis antigens: CTAG2 (NY-ESO-2), MAGEA1, SSX1, and SSX4. Thirty-five patients, who received an autologous vaccine, followed by ipilimumab for progressive disease, had a significantly improved 3-year survival of 46% compared with 19% in nonvaccinated patients treated with ipilimumab alone (p = 0.007). Conclusion. Improved survival in patients attaining a strong DTH and increased response rate with subsequent ipilimumab suggests that the autologous vaccine confers protective immunity. ĂŻÂżÂœ 2016 Michal Lotem et al

    Targeting ion channels for cancer treatment : current progress and future challenges

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    Statistically induced chunking recall: A memory‐based approach to statistical learning

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    The computations involved in statistical learning have long been debated. Here, we build on work suggesting that a basic memory process, chunking , may account for the processing of statistical regularities into larger units. Drawing on methods from the memory literature, we developed a novel paradigm to test statistical learning by leveraging a robust phenomenon observed in serial recall tasks: that short‐term memory is fundamentally shaped by long‐term distributional learning. In the statistically induced chunking recall (SICR) task, participants are exposed to an artificial language, using a standard statistical learning exposure phase. Afterward, they recall strings of syllables that either follow the statistics of the artificial language or comprise the same syllables presented in a random order. We hypothesized that if individuals had chunked the artificial language into word‐like units, then the statistically structured items would be more accurately recalled relative to the random controls. Our results demonstrate that SICR effectively captures learning in both the auditory and visual modalities, with participants displaying significantly improved recall of the statistically structured items, and even recall specific trigram chunks from the input. SICR also exhibits greater test–retest reliability in the auditory modality and sensitivity to individual differences in both modalities than the standard two‐alternative forced‐choice task. These results thereby provide key empirical support to the chunking account of statistical learning and contribute a valuable new tool to the literature

    Bridging artificial and natural language learning: Comparing processing- and reflection-based measures of learning

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    A common assumption in the cognitive sciences is that artificial and natural language learning rely on shared mechanisms. However, attempts to bridge the two have yielded ambiguous results. We suggest that an empirical disconnect between the computations employed during learning and the methods employed at test may explain these mixed results. Further, we propose statistically-based chunking as a potential computational link between artificial and natural language learning. We compare the acquisition of non-adjacent dependencies to that of natural language structure using two types of tasks: reflection-based 2AFC measures, and processing-based recall measures, the latter being more computationally analogous to the processes used during language acquisition. Our results demonstrate that task-type significantly influences the correlations observed between artificial and natural language acquisition, with reflection-based and processing-based measures correlating within – but not across – task-type. These findings have fundamental implications for artificial-to-natural language comparisons, both methodologically and theoretically
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