Phrase parsing in a second language as indexed by the closure positive shift: The impact of language experience and acoustic cue salience.

Despite the importance of prosodic processing in utterance parsing, a majority of studies investigating boundary localization in a second language focus on word segmentation. The goal of the present study was to investigate the parsing of phrase boundaries in first and second languages from different prosodic typologies (stress-timed vs. syllable-timed). Fifty English-French bilingual adults who varied in native language (French or English) and second language proficiency listened to English and French utterances with different prosodic structures while event-related brain potentials were recorded. The utterances were built around target words presented either in phrase-final position (bearing phrase-final lengthening) or in penultimate position. Each participant listened to both English and French stimuli, providing data in their native language (used as reference) and their second language. Target words in phrase-final position elicited closure positive shifts across listeners in both languages, regardless of the language-specific acoustic cues associated with phrase-final lengthening (shorter phrase-final lengthening in English compared to French). Interestingly, directional effects were observed, where learning to parse English as a second language in a native-like manner seemed to require a higher proficiency level than learning to parse French as a second language. This pattern of results supports the idea that L2 listeners need to learn to recognize L2-specific phrase-final lengthening regardless of the apparent similarity across languages and that some language combinations might present greater challenges than others.

Spoken Word Segmentation in First and Second Language: When ERP and Behavioral Measures Diverge.

Previous studies of word segmentation in a second language have yielded equivocal results. This is not surprising given the differences in the bilingual experience and proficiency of the participants and the varied experimental designs that have been used. The present study tried to account for a number of relevant variables to determine if bilingual listeners are able to use native-like word segmentation strategies. Here, 61 French-English bilingual adults who varied in L1 (French or English) and language dominance took part in an audiovisual integration task while event-related brain potentials (ERPs) were recorded. Participants listened to sentences built around ambiguous syllable strings (which could be disambiguated based on different word segmentation patterns), during which an illustration was presented on screen. Participants were asked to determine if the illustration was related to the heard utterance or not. Each participant listened to both English and French utterances, providing segmentation patterns that included both their native language (used as reference) and their L2. Interestingly, different patterns of results were observed in the event-related potentials (online) and behavioral (offline) results, suggesting that L2 participants showed signs of being able to adapt their segmentation strategies to the specifics of the L2 (online ERP results), but that the extent of the adaptation varied as a function of listeners' language experience (offline behavioral results).

Erlotinib-cisplatin combination inhibits growth and angiogenesis through c-MYC and HIF-1α in EGFR-mutated lung cancer in vitro and in vivo.

Combination treatment for non-small cell lung cancer (NSCLC) is becoming more popular due to the anticipation that it may be more effective than single drug treatment. In addition, there are efforts to genetically screen patients for specific mutations in light of attempting to administer specific anticancer agents that are most effective. In this study, we evaluate the anticancer and anti-angiogenic effects of low dose erlotinib-cisplatin combination in NSCLC in vitro and in vivo. In NSCLC cells harboring epidermal growth factor receptor (EGFR) mutations, combination erlotinib-cisplatin treatment led to synergistic cell death, but there was minimal efficacy in NSCLC cells with wild-type EGFR. In xenograft models, combination treatment also demonstrated greater inhibition of tumor growth compared to individual treatment. The anti-tumor effect observed was secondary to the targeting of angiogenesis, evidenced by decreased vascular endothelial growth factor (VEGF) levels and decreased levels of CD31 and microvessel density. Combination treatment targets angiogenesis through down-regulation of the c-MYC/hypoxia inducible factor 1-alpha (HIF-1α) pathway. In fact, cell lines with EGFR exon 19 deletions expressed high basal levels of c-MYC and HIF-1α and correlate with robust responses to combination treatment. These results suggest that low dose erlotinib-cisplatin combination exhibits its anti-tumor activity by targeting angiogenesis through the modulation of the c-MYC/HIF-1α/VEGF pathway in NSCLC with EGFR exon 19 deletions. These findings may have significant clinical implications in patients with tumors harboring EGFR exon 19 deletions as they may be particularly sensitive to this regimen.

Combination erlotinib-cisplatin and Atg3-mediated autophagy in erlotinib resistant lung cancer.

Tyrosine kinase inhibitors such as erlotinib are commonly used as a therapeutic agent against cancer due to its relatively low side-effect profile and, at times, greater efficacy. However, erlotinib resistance (ER) in non-small cell lung cancer is being recognized as a major problem. Therefore, understanding the mechanism behind ER and developing effective regimens are needed. Autophagy's role in cancer has been controversial and remains unclear. In this study, we examined the effectiveness of low dose erlotinib-cisplatin combination in erlotinib resistant lung adenocarcinoma (ERPC9) cells and the role of autophagy in ER. ERPC9 cells were established from erlotinib sensitive PC9 cells. Appropriate treatments were done over two days and cell survival was quantified with Alamar Blue assay. LC3II and regulatory proteins of autophagy were measured by western blot. Small interfering RNA (siRNA) was utilized to inhibit translation of the protein of interest. In ERPC9 cells, combination treatment induced synergistic cell death and a significant decrease in autophagy. At baseline, ERPC9 cells had a significantly higher LC3II and lower p-mTOR levels compared to PC9 cells. The addition of rapamycin increased resistance and 3-methyladenine sensitized ERPC9 cells, indicating autophagy may be acting as a protective mechanism. Further examination revealed that ERPC9 cells harbored high baseline Atg3 levels. The high basal Atg3 was targeted and significantly lowered with combination treatment. siRNA transfection of Atg3 resulted in the reversal of ER; 42.0% more cells died in erlotinib-alone treatment with transfection compared to non-transfected ERPC9 cells. We reveal a novel role for Atg3 in the promotion of ER as the inhibition of Atg3 translation was able to result in the re-sensitization of ERPC9 cells to erlotinib-alone treatment. Also, we demonstrate that combination erlotinib-cisplatin is an effective treatment against erlotinib resistant cancer by targeting (down-regulating) Atg3 mediated autophagy and induction of apoptotic cell death.

Complications and perioperative factors associated with learning the technique of minimally invasive transforaminal lumbar interbody fusion (TLIF).

Before the advent of minimally invasive spine surgery (MIS), open transforaminal lumbar interbody fusion (TLIF) was performed to treat spondylosis, spondylolisthesis, and spondylolysis. Minimally invasive TLIF has recently become more popular based upon the premise that a smaller, less traumatic incision should afford better recovery and outcomes. However, the learning curve associated with this technique must be considered. To analyze the perioperative factors associated with the learning curve in patients who underwent MIS TLIF versus open TLIF, we identified 22 patients who underwent TLIF from 2005 to 2008 within levels L4-S1 by the senior author (D.C.). Patients were subdivided into two groups according to whether they underwent: (i) MIS TLIF (10 patients, the first MIS TLIF procedures performed by D.C.); or (ii) open TLIF (12 patients). Preoperative, perioperative and postoperative factors were evaluated. Patients who underwent MIS TLIF had a statistically significant lower intraoperative transfusion rate, and rate of required postoperative surgical drains; and shorter periods of required drainage, and time to ambulation. However, the MIS TLIF group tended to have a higher rate of complications, which might have been associated with the learning curve. Both groups had a minimum of 1-year follow-up.

Minimally invasive compared to open microdiscectomy for lumbar disc herniation.

Before the advent of minimally invasive surgery for microdiscectomy, an open microdiscectomy had been the standard surgical intervention. Minimally invasive techniques have recently become more popular based upon the premise that smaller, less traumatic incisions should afford better recovery times and outcomes. From 2005 to 2008 we analyzed the outcomes of 25 patients who received an open microdiscectomy compared to 20 patients who received a minimally invasive microdiscectomy by the senior author (DC) in the lumbar region for disc herniation. A retrospective analysis was performed by carefully reviewing medical records for perioperative and immediate postoperative outcomes, and clinical follow-up was obtained either in the clinic or by telephone. There were no statistically significant differences between the minimally invasive and open groups in terms of operative time, length of stay, neurological outcome, complication rate, or change in pain score (pain improvement).

The transpedicular approach compared with the anterior approach: an analysis of 80 thoracolumbar corpectomies.

OBJECT: Whereas standard anterior approaches for thoracolumbar corpectomies have commonly been used, the transpedicular technique is increasingly used to perform corpectomies from a posterior approach. The authors conducted a study to analyze whether there was a difference in outcomes by comparing transpedicular corpectomies to standard anterior thoracolumbar corpectomies. METHODS: The senior author performed thoracolumbar corpectomies in 80 patients between 2004 and 2008. The authors reviewed medical records and follow-up data, consisting of clinic visits, radiographs, or telephone interviews. Neurological outcome, complications, operative times, revision surgery rates, and estimated blood loss (EBL) were evaluated. RESULTS: Thirty-four patients underwent transpedicular corpectomies, and 46 patients underwent anterior thoracolumbar approaches. Single-level transpedicular corpectomies appear to be comparable to anterior-only corpectomies in terms of EBL, operative time, and complication rates. There was a higher complication rate, increased EBL, and longer operative time with anterior-posterior corpectomies compared with transpedicular corpectomies. Patients undergoing transpedicular corpectomies had a greater recovery of neurological function than those in whom anterior-approach corpectomies were performed. CONCLUSIONS: The transpedicular corpectomy appears to have a comparable morbidity rate to anterior-only corpectomies, but its morbidity rate is lower than that of anterior-posterior corpectomies.