Spanish Task Research Articles

L2 within-language morphological competition during spoken word recognition

ABSTRACT Bilinguals recognize words with shared morphology and phonology cross-linguistically (i.e., cognates) faster than words that do not have these characteristics. Moreover, higher phonological overlap in cognates enhances the effects, which suggests that phonology eases word recognition. However, it is currently unclear whether words compete purely morphologically before spoken word recognition within language and whether proficiency in the L2 modulates the degree of morphological competition. Spanish monolinguals and English L2 learners of Spanish with varying L2 proficiency completed an auditory lexical decision task in Spanish. Stimuli were phonological sequences of Spanish words prior to a recognition point (e.g., /mark/ in /marko/) whose activated cohorts were minimal pairs. Some pairs were morphologically related (e.g., huerto ‘vegetable patch’ versus huerta ‘vegetable garden’), whereas some others had no morphological relationship (e.g., marco ‘frame’ versus marca ‘brand’). Results showed that both groups processed solely phonological competitors in a similar way as they did with morphological competitors. Taken together, these findings suggest that morphological relatedness does not modulate either L1 or L2 spoken word recognition prior to a recognition point when speakers listen to words in absence of context. In addition, the findings suggest that the L2 recognition architecture is qualitatively similar to that of native speakers.

Orthography affects L1 and L2 speech perception but not production in early bilinguals

AbstractOrthography plays a crucial role in L2 learning, which generally relies on both oral and written input. We examine whether incongruencies between L1 and L2 grapheme-phoneme correspondences influence bilingual speech perception and production, even when both languages have been acquired in early childhood before reading acquisition. Spanish–Basque and Basque–Spanish early bilinguals performed an auditory lexical decision task including Basque pseudowords created by replacing Basque /s̻/ with Spanish /θ/. These distinct phonemes take the same orthographic form, <z>. Participants also completed reading-aloud tasks in Basque and Spanish to test whether speech sounds with the same orthographic form were produced similarly in the two languages. Results for both groups showed orthography had strong effects on speech perception but no effects on speech production. Taken together, these findings suggest that orthography plays a crucial role in the speech system of early bilinguals but does not automatically lead to non-native production.

Flunking the Spanish test: Television portrayals of personal responsibility and language shift in heritage learners

ABSTRACT The language practices of Heritage Learners (HLs) of Spanish are frequently regulated and stigmatized in academic and community settings when their Spanish is perceived as deficient. By ignoring institutional structures that accelerate Spanish loss, the “inadequacy” of Latinxs’ Spanish is regularly perceived to be the fault of individuals or families. This study examines language ideologies that emerge in popular television shows for pre-teens (i.e. tweens), revealing that HLs are regularly portrayed as failing Spanish in academic settings and unable to complete everyday communicative tasks in Spanish. When their lack of Spanish is woven into the narrative of a sitcom problem, the resolution of these conflicts leads youth, parents, and grandparents to reflect on their individual responsibility to maintain the language and culture, which reinforces a neoliberal ideology of family responsibility for language maintenance.

Morphological processing and individual frequency effects in L1 and L2 Spanish

Surface frequency and proficiency modulate visual morphological processing in second language (L2) learners, but less is known about auditory morphological processing. Moreover, working memory (WM) affects morphosyntactic processing, but it is unclear whether it also modulates word structure processing. In the present study, Spanish monolinguals and beginner and advanced L2 learners of Spanish completed an auditory lexical decision task in Spanish containing verbs varying in morphological complexity, an individual lexical frequency task, and a working memory task. Beginner L2 learners needed more time to process infrequent morphologically complex words, but monolinguals and advanced L2 learners were unaffected by morphological complexity or surface frequency. Also, WM did not modulate morphological processing. Taken together, the findings suggest a dual-route mechanism at initial stages of L2 acquisition and a whole-word route for Spanish monolinguals and advanced L2 learners. The findings also support the extension of dual-route models to L2 populations and suggest that the selection of a morphological processing route results from linguistic rather than cognitive reasons.

Contribution of Nonverbal Cognitive Skills on Bilingual Children’s Grammatical Performance: Influence of Exposure, Task Type, and Language of Assessment

This study explores the contribution of nonverbal working memory and processing speed on bilingual children’s morphosyntactic knowledge, after controlling for language exposure. Participants include 307 Spanish–English bilinguals in Kindergarten, second, and fourth grade (mean age = 7;8, SD = 18 months). Morphosyntactic knowledge in English and Spanish was measured using two separate language tasks: a cloze task and a narrative language task. In a series of four hierarchical linear regressions predicting cloze and narrative performance in English and Spanish, we evaluate the proportion of variance explained after adding (a) English exposure, (b) processing speed and working memory, and (c) interaction terms to the model. The results reveal the differential contribution of nonverbal cognitive skills across English and Spanish. Cognition was not significantly related to performance on either grammatical cloze or narrative tasks in Spanish. Narrative tasks in English were significantly predicted by processing speed, after controlling for age and exposure. Grammatical cloze tasks in English posed an additional cognitive demand on working memory. The findings suggest that cognitive demands vary for bilinguals based on the language of assessment and the task.

An exploratory study on pro-drop in a written description task in L2 Spanish

Abstract The present article aims at investigating the pro-drop phenomenon in L2 Spanish. The phenomenon of pro-drop or null subject is a typological feature of some languages, which are characterized by an implicit subject in cases of topic continuity. More specifically, behaviour regarding subject (dis)continuity in Spanish differs from French. This paper will offer a contrastive analysis on subject realisation by French learners of L2 Spanish compared to L1 Spanish speakers. So, the goal of this pilot study is to see if a different functioning in pro-drop in the mother tongue also influences the L2. The study is based upon a written description task presented to the two groups of participants: the experimental group of French mother tongue L2 Spanish language learners and the control group of Spanish native speakers.

1174P RESUNET (GETNE-2016-01): A phase II study to evaluate the efficacy and safety of the rechallenge with sunitinib in G1/G2 pancreatic neuroendocrine tumours (pNET). A Spanish Task Force Group in neuroendocrine and endocrine tumours (GETNE) study

1174P RESUNET (GETNE-2016-01): A phase II study to evaluate the efficacy and safety of the rechallenge with sunitinib in G1/G2 pancreatic neuroendocrine tumours (pNET). A Spanish Task Force Group in neuroendocrine and endocrine tumours (GETNE) study

Neural-based approach for Cancer Named Entity Recognition task in Spanish

Neural-based approach for Cancer Named Entity Recognition task in Spanish

Molecular correlation of the activity of evofosfamide (EVO) in combination with sunitinib (SUN) in pancreatic Neuroendocrine Tumors (pNETs) in the SUNEVO GETNE Trial.

e16706 Background: MEN1, DAXX, ATRX, and PI3K/AKT/mTOR pathway genes are frequently mutated in pNETs. Sunitinib is approved and widely used in the metastatic setting but unfortunately, no validated predictive biomarker has been identified to guide therapy yet. The SUNEVO phase II trial of the Spanish Task Force Group for Neuroendocrine and Endocrine Tumours (GETNE) trial combined the pro-drug of EVO under SUN-induced hypoxic conditions. Methods: We performed an exploratory analysis aimed to identify somatic mutations associated with the clinical benefit of pNET patients treated with SUN+EVO combination. Seventeen treatment-naïve pts with pNETS were included in the SUNEVO trial, and 4 (23.5%) achieved a partial response (by RECIST 1.1). Tumor DNA from 10 FFPE tumor samples were successfully sequenced with an enrichment panel (Nimblegen, Roche) including 42 cancer-related genes and TERT promoter region. Median coverage was 793x. Coding non-synonymous and loss-of-function variants were considered for the analysis. Final analysis included tumor samples from the 10 patients with NGS results. Results: Somatic mutations were found in MEN1 (70%), DAXX (30%), ATRX (20%), SETD2 (20%) and PTEN (10%). Mutations in the telomere maintenance genes DAXX and ATRX were concordant with mutual exclusivity. The loss of MEN1 was associated with a greater number of mutations (p = 0.019). Patients with complete and partial response showed heterogeneous genetic profiles. Conclusions: The molecular alterations of the patients in the SUNEVO trial were consistent with those previously described for metastatic pNETs. No clear association between molecular defects and treatment response was found. Clinical trial information: NCT02402062 .

An Exploratory Study of the Effect of Spanish Immersion Education on the Acquisition of Pronominal Subjects in Child Heritage Speakers

Studies have found that aspects of grammar that lie at the syntax–pragmatics interface, such as the use of pronominal subjects in null-subject languages, are likely to undergo cross-linguistic influence in bilingual speakers. This study contributes to our understanding of the role of Spanish immersion academic instruction on the comprehension of null subjects in English-dominant, Spanish-heritage children living in the United States. Two groups of bilingual children aged 4 to 7 (those attending a Spanish immersion school and those not) completed an acceptability judgment task in both English and Spanish. English monolingual children and monolingually raised Spanish children of the same ages also completed the task in their respective languages. The findings revealed that children in the Spanish immersion school performed on par with their monolingual peers in Spanish, but accepted significantly more ungrammatical null subjects in English than the other groups. These results suggest that immersion schooling plays a role in extending the English null subject stage in bilingual children due to competing input and cross-linguistic influence.

Perceptual salience of derivational suffixes in visual word recognition.

This study analyzes the role of derivational suffixes in visual word recognition, tracking the eye movements of 31 participants in a sentence-reading task in Spanish. Perceptual salience of suffixes was operationalized as the proportion of letters represented by the suffixes with respect to the full words, that is, we relate the number of letters comprising the suffixes to the number of letters in the words in which they appear. The results reveal a significant role in first fixation duration of both word frequency - the more frequent the word, the shorter the fixations, and perceptual salience - the more salient the suffix, the longer the fixations. Moreover, in gaze duration, our results show a main effect of word length - the longer the word, the longer the fixations; word frequency; and significant interactions between word frequency and perceptual salience of suffixes on the one hand - the effect of word frequency is only significant when perceptual salience of suffixes is high, and between word frequency and word length on the other hand - the frequency effect decreases as word length increases. Overall results are interpreted in the light of the dual route models by which full-form and morphological processing interactively cooperate in visual word recognition.

Integrated curriculum design: Outcomes of a two-week Spanish intensive course for nursing students

This article analyzes the outcomes of an intensive Spanish course for nursing students of various Spanish language abilities. The course objectives were to enable the students to conduct a nursing assessment interview and data gathering in Spanish, as well as providing instructions and recording information for vital signs and a head-to-toe physical exam. Treating these interactions as standard communicative frames, utilizing Goffman’s (1974) schema, guided the course development. Vocabulary and grammar were restricted to the needs of the assigned tasks, and concentrated on speaking and receptive abilities, not on writing or reading. The course was successful in achieving the stated course objectives, and students demonstrated basic communication skills and the ability to perform the assigned tasks in Spanish at the end of the course.

1387P - Differences in multikinase inhibitors (MKI) toxicity profile according to gender. A pooled analysis of three phase II trials with lenvatinib, pazopanib and sorafenib in patients (pts) with advanced gastroenteropancreatic (GEP) neuroendocrine tumours (NETs)

BackgroundThere is a dearth of understanding of gender influence in targeted therapies toxicity. Increasing evidence suggests a possible different toxicity profile according to gender, but mostly retrospective studies in common tumors. Currently, data from prospective studies are minimal. In the present study, we will review MKI toxicity profiles according to gender in pts with NETs in three clinical trials. MethodsMulticenter open-label phase II studies TALENT, PAZONET and GETNE0801 included pts with advanced GEP NETs treated with lenvatinib, pazopanib, and sorafenib-bevacizumab respectively. All studies were performed by the Spanish Task Force Group for Neuroendocrine Tumors (GETNE). All pts were included in the review, considering all toxicity grades with an incidence higher than 5% for the univariate analysis. Bevacizumab specific toxicities were excluded in patients from GETNE0801 trial. Additionally, all grade 3-4 toxicities were analyzed separately. Results199 pts (46.23% female) with 1349 adverse events (AEs) (12.23% G3-4) divided into 125 categories were included. In female patients, nausea/vomiting, skin disorders (excluding palmar-plantar erythrodysesthesia), liver alterations (including transaminase and bilirubin), headache, pyrexia, hair disorders and dizziness were significantly more common (Table). The only toxicity with a higher incidence in men was dysphonia (OR 0.42, 95% CI 0.2-0.9, p0.02). The only G3-4 toxicity significantly more frequent in women was liver toxicity (20.65% vs. 7.55%, OR 3.18, p0.009).Table: 1387PTable: 1387PToxicity (all grades)Women (%)Men (%)Difference (%)Odds Ratio (95% CI)pNausea/Vomiting63.0444.86182.090.01Skin disorders60.8745.79151.840.03Liver toxicity57.6130.84263.040.0002Headache28.2612.15162.840.005Pyrexia17.395.61113.440.01Hair disorders20.658.41122.830.01Dizziness17.396.54103.000.02Dysphonia16.3037.38210.320.001 ConclusionsIn our study, we observed significant differences in toxicity AEs by gender, especially in women with seven increased toxicities. A different approach in toxicity management should be adopted based on gender in pts with GEP NETs treated with MKI. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureJ. Hernando Cubero: Speaker Bureau / Expert testimony: Eisai, Ipsen, Roche, Angelini, ; Travel / Accommodation / Expenses: Ipsen, Novartis, AAA, Roche, AstraZeneca, Eisai. E. Grande: Speaker Bureau / Expert testimony: Pfizer, Ipsen, BMS, Eisai, Roche, MSD, Sanofi, Adacap, Novartis, EUSA Pharma, Pierre Fabre, Lexicon, Celgene; Research grant / Funding (institution): MSD, Roche. T. Ibrahim: Advisory / Consultancy: Eisai; Research grant / Funding (institution): Novartis; Travel / Accommodation / Expenses: Ipsen, PharmaMar, Novartis. J.W. Valle: Advisory / Consultancy: Abbott, Agios, AstraZeneca, Baxalta, Bioven, Celgene, Delcath, Genoscience Pharma, Incyte, Ipsen, Keocyt, Lilly, Merck, MidaTech, Mundipharma, Novartis, NuCana, PCI Biotech, Pfizer, Pieris Pharmaceuticals, QED Pharmaceuticals; Speaker Bureau / Expert testimony: Abbott, Celgene, Ipsen, Novartis, Pfizer, Sirtex; Travel / Accommodation / Expenses: Celgene, Ipsen, Novartis, NuCana. V. Alonso: Advisory / Consultancy: Amgen, Roche, Merck, Servier, Sanofi, Ipsen, Bayer, Novartis. R. Manneh Kopp: Speaker Bureau / Expert testimony: Pfizer, Ipsen, BMS, Roche, MSD, Sanofi, Novartis; Research grant / Funding (institution): MSD, Roche, BMS. R. Salazar: Advisory / Consultancy: VCN-BCN, Agendia, Guardant Health, Roche Diagnostics, Ferrer, Pfizer, Novartis, Ipsen, Amgen, Merck, Roche Farma, Lylli, MSD; Speaker Bureau / Expert testimony: Pfizer, Amgen, Novartis, Merck, MSD, AZD, Celgene,. J. Capdevila: Honoraria (self): Novartis, Pfier, Ipsen, Exelixis, Bayer, Eisai, AAA, Amgen, Sanofi, Merck; Research grant / Funding (institution): Eisai, Novartis, Ipsen, AstraZeneca, Pfier, AAA. All other authors have declared no conflicts of interest.

1384PD - SUNitinib with EVOfosfamide (TH-302) for G1/G2 metastatic pancreatic neuroendocrine tumours (pNETs) naïve for systemic treatment. The SUNEVO phase II trial of the Spanish task force group for neuroendocrine and endocrine tumours (GETNE)

BackgroundSunitinib (SUN) is approved for the treatment of advanced progressive pNETs. Hypoxia induced by SUN could foster the activation of the prodrug evofosfamide (EVO), designed to release the DNA alkylator bromo-isophosphoramide mustard under hypoxic conditions. The SUNEVO trial seeks to exploit the potential synergy of SUN + EVO in advanced pNETs. MethodsPhase-II, single-arm, multicenter trial that included 17 patients (pts) with metastatic G1/G2 pNETS naive for systemic treatment (tx) other than somatostatin analogues (SSA). Tx consisted on EVO 340mg/m2 on days 8, 15 and 22 every 4 weeks (q4w), and sunitinib 37.5mg/day continuously. Objective response rate (ORR) was selected as the primary endpoint and evaluated q8w by RECIST 1.1. ResultsMedian age was 62.4 years, 41.2% had prior SSA, 47% had a Ki-67 >10%, 70.6% had liver involvement. Patients received a median of 5 (1-21) and 4 (0-21) cycles of SUN and EVO, respectively. After a median follow-up time of 15.7 months (m), 23.5% achieved a partial (N=3) or complete response (N=1), 11 pts had stable disease (64.7%) and 1pt (5.3%) had progressive disease as best response. Median time to response was 1.9m (1.4-8.8) and duration of response was 18.5 m (4.2-38.3). Median PFS was 10.3 m (2.6-18.0). Treatment-related adverse events of >G3 or were observed in 52.9% pts, being the most frequent being neutropenia (18.8%), hypertension (12.5%), ALT increase (12.5%), thrombopenia (6.3%), and fatigue (6.3%). 4 pts (26.7%) discontinued at least one drug due toxicity. ConclusionsSUN + EVO is active in pts with advanced pNETs, but the toxicity profile of the combination negatively affects tolerability. Biomarker analyses to select patients most likely to benefit from this therapy are ongoing. Clinical trial identificationEUDRACT Number: 2014-004072-30 Approval date for the trial: 22-January-2015. Editorial acknowledgementMfar Clinical Research S.L. Legal entity responsible for the studyGrupo Español de Tumores Neuroendocrinos y Endocrinos (GETNE). FundingMolecular Templates Inc. and Pfizer Inc. DisclosureE. Grande: Speaker Bureau / Expert testimony, Public speaking and expert: Pfizer, Ipsen, BMS, Eisai, Roche, MSD, Sanofi-Genzyme, Adacap, Novartis, Eusa Pharma, Pierre Fabre, Lexicon, Celgene; Leadership role, Principal Investigator: AstraZeneca, Pfizer, Ipsen, Mtem/Threshold Lexicon; Honoraria (institution), Medical Education Grant: MSD, Roche; Non-remunerated activity/ies, Advasory Board Member: Enets; Non-remunerated activity/ies, Directory Board Member: Getne; Non-remunerated activity/ies, Directory Board Member: Gethi. C. Lopez: Honoraria (self): Pfizer, Ipsen, Roche; Advisory / Consultancy: Pfizer, Ipsen, Roche; Research grant / Funding (self): Pfizer, Ipsen, Roche; Travel / Accommodation / Expenses: Pfizer, Ipsen, Roche; Honoraria (self): Novartis. T. Alonso Gordoa: Research grant / Funding (self): Roche; Travel / Accommodation / Expenses: Sanofi, Pfizer. J. Capdevila: Advisory / Consultancy: Eisai, Bayer, Exelixis, Novartis, Pfizer, Adacap, Merck Serono; Speaker Bureau / Expert testimony: Eisai, Bayer, Exelis, Ipsen, Novartis, Pfizer, Adacap, Merck Serono; Research grant / Funding (self): Eisai, Exelixis, Adacap, AstraZeneca, Novartis; Travel / Accommodation / Expenses: Ipsen, Pfizer, Eisai. A. Teulé: Advisory / Consultancy: Pfizer, Ipsen, Novartis. I. Sevilla: Advisory / Consultancy: Ipsen, Novartis, Pfeizer, Lilly; Travel / Accommodation / Expenses: Ipsen. P. Gajate: Advisory / Consultancy: IPSSEN; Speaker Bureau / Expert testimony: Ipsen; Travel / Accommodation / Expenses: Ipsen. J. Molina-Cerrillo: Speaker Bureau / Expert testimony: Ipsen, Janssen. J. Hernando Cubero: Speaker Bureau / Expert testimony: Eisai, Ipsen, Roche, Angelini Pharma; Travel / Accommodation / Expenses: Ipsen, Novartis, Advanced Accekeratir Applications, Roche, AstraZeneca, Eisai. R. Garcia-Carbonero: Honoraria (self): Ipsen, Roche, Sanofi, BMS, Servier, Novartis, Pfizer, Merck, PharmaMar, Adacap; Honoraria (self), An intermediate Family Member: Merck, PharmaMar, Roche, BMS, AZ, Lilly, Boerhinger, Gilead Sc, Servier, Sysmex; Advisory / Consultancy: Ipsen, Novartis, Pfizer, AAA; Speaker Bureau / Expert testimony: Ipsen, Pfizer; Research grant / Funding (institution): Pfizer, BMS, MSD, AstraZeneca; Travel / Accommodation / Expenses: Roche, Merck. All other authors have declared no conflicts of interest.

Can gapping be embedded? Experimental evidence from Spanish

This paper discusses the No Embedding Constraint, considered to be a strong syntactic constraint on gapping and a diagnostic for this ellipsis type. As shown by two acceptability judgments tasks in Spanish, the assumptions related to the No Embedding Constraint are not borne out by our experimental results. Embedded gapping is acceptable in Spanish, and seems to be governed by a (more general) semantic constraint. Specifically, some predicates embed more easily than others, confirming, on the one hand, the asymmetry between non-factive and factive predicates, and, on the other hand, the dichotomy between semi-factive and true factive predicates. Embedded gapping and embedded coordinated clauses in general are thus sensitive to the semantic class of the embedding predicate. We argue that our data on embedded gapping in Spanish constitute a challenge for any Small Conjunct Gapping approach (in terms of subclausal/low coordination) and give support to a Large Conjunct Gapping approach (in terms of clausal/high coordination). In this paper, we adopt a constructional fragment-based analysis of gapping, which treats non-embedded and embedded gapping uniformly. More generally, this paper suggests that gapping is more similar to other ellipsis types than has been traditionally assumed.

Verbal fluency in Mexican Spanish-speaking subjects with high educational level: Ranking of letters and semantic categories

ABSTRACTIntroduction: Verbal fluency tasks are useful tools in clinical practice and research studies across languages and contexts, but specific data obtained using Spanish phonological tasks and semantic tasks with different levels of difficulty are lacking. The present study aimed to determine the difficulty level of a phonological tasks and semantic tasks among Spanish-speakers.Method: Both tasks were ordered across five difficulty levels based on the frequency of use in Mexican Spanish (phonological) and the number of elements given by a group of participants (semantic). One hundred healthy Mexican Spanish-speaking participants (aged 24–63 years; 55 females) were presented with five phonological and five semantic categories. The participants also underwent a neuropsychological test and sociodemographic interview. The number of words correctly produced in each category within one minute was calculated. An ANOVA and a Kruskal-Wallis analysis were conducted in order to know if there were different levels of difficulty in the tasks. Additionally, correlation analyzes were performed to test the effect of the sociodemographic and cognitive variables on the participants’ responses.Results: According to the analyzes, there were different levels of difficulty in the categories; P was the easiest and O was the most difficult category in the phonological tasks, and body parts and precious stones were the easiest and most difficult, respectively, in the semantic tasks. Age had a negative correlation with four-legged animals and a positive correlation with O; Positive correlations were also found between education and professions, vegetables, and alcoholic beverages; and between IQ and D, N, musical instruments, sports, vegetables, and trees.Conclusions: Both tasks offer categories with different level of difficulty based on the performance of a highly educated Mexican population. These data may be useful for clinical and research purposes.

Bilingual Phonological Awareness: Construct Validation in Grade 1 Spanish-Speaking English Learners.

This study investigated the dimensionality of bilingual phonological awareness (PA) in English and Spanish by replicating a kindergarten model in Grade 1, and presents alternatives to modeling clustered data. English and Spanish tasks were analyzed from previously collected samples totaling 1,586 first grade Spanish-speaking English learners. Four distinct approaches to confirmatory factor analysis (CFA) models were examined: (a) uncentered student-level data, (b) student-level data centered at the classroom means, (c) classroom-level data, and (d) multilevel CFA. Results indicated that while the multilevel CFA provided the most comprehensive view of the data, the multi-level student-level estimates were not appreciably different from estimates based on student-level data centered at the classroom means, and multi-level classroom-level estimates were comparable to estimates based on the analysis of classroom means. Importantly, English and Spanish PA were statistically separable at the student-level, but minimally distinct (r=.86) and slightly less correlated than what has been reported for kindergarten (r=.93). At the classroom level, the correlation was moderate (r=.51), and substantially reduced compared to kindergarten (r=.83). The distinction at the classroom-level between kindergarten and Grade 1 implies that instruction differentiates the abilities across languages at the classroom-level, but less so at the student-level.

Impact of gender on multikinase inhibitors (MKIs) toxicity in patients (pts) with advanced pancreatic and gastrointestinal neuroendocrine tumors (NETs): A pooled analysis of two phase II trials with pazopanib and lenvatinib.

4109 Background: Retrospective data in some cancer types suggested a possible different toxicity profile with chemotherapy and targeted therapies according to gender. However, data from prospective studies are still very limited, especially in infrequent tumors such as NETs. Methods: Pts with advanced pancreatic and gastrointestinal NETs treated with pazopanib or lenvatinib in the multicenter open-label phase II studies PAZONET and TALENT respectively, were included in the analysis. Both studies were performed by Spanish Task Force Group for Neuroendocrine Tumors (GETNE). All toxicity grades with an incidence higher than 5% were considered for univariate review. Additionally, all grade 3-4 toxicities were analyzed separately. Results: 155 pts (47.7% female) with 1213 adverse events (AEs) (20% G3-4) divided in 121 categories were included. In female patients, liver toxicity, headache, pyrexia, nausea/vomiting, hair/skin disorders and dizziness were significantly more common (table). The only toxicity with higher incidence in men was dysphonia (OR 0.42, 95% CI 0.2-0.9, p 0.02). There were no gender differences in grade 3-4 toxicities. Conclusions: We observed significant differences in toxicity AEs by gender in two prospective phase II studies with MKIs in NETs patients. Potential different approach to manage toxicity may be adopted based on gender. [Table: see text]

The SUNEVO (GETNE-1408) trial to evaluate the activity and safety of thecombination of sunitinib with evofosfamide (TH-302) in patients with G1/G2 metastatic pancreatic neuroendocrine tumours (pNETs) naïve forsystemic treatment: A phase II study of the Spanish Task Force Group for Neuroendocrine and Endocrine Tumors (GETNE).

4105 Background: Angiogenesis plays an important role in tumorigenesis and progression of pNETs. Evofosfamide (EVO) is a DNA alkylator prodrug that selectively activates under hypoxia. Sunitinib as monotherapy shows a wide range of responses (9-24%) in similar populations. We hypothesized that sunitinib-induced hypoxia might increase the cytotoxic activity of EVO in patients with metastatic pNETS and naïve for systemic treatment other than somatostatin analogues (SSA). Methods: This is a phase-II, single-arm, and multicenter trial of EVO (340mg/m2 on days 8, 15 and 22 every 4 weeks) and sunitinib (37.5mg/day continuously). Primary endpoint was Objective Response Rate (ORR) by RECIST v1.1 assessed every 8 weeks. A Simon two-stage optimal design was used, considering a minimum of 3 responses in the first 18 pts in order to start with the second stage (power = 0.80, alpha = 0.05). Results: Between May/2015 and May/2018, 17 pts were included (median age was 62.4 y.o). Prior SSA was reported in 7 (41.2%) pts and 8 (47.1%) had a Ki-67 > 10%. There were 2 responders (11.8%; n = 1 complete and n = 1 partial response); stable disease was observed in 76.5%. Median (range) PFS and duration of response were 10.4 months (m) (2.9-17.9m) and, respectively 24.4m (13.7-35.2m), respectively. Grade 3 or 4 adverse events occurred in 11 (64.7%) pts, being neutropenia (33.3%), fatigue (16.7%), thrombocytopenia (11.1%), hand-foot syndrome (5.6%), and pancreatitis (5.6%) the most frequent. Toxicity led to treatment discontinuation in 5 (38.5%) pts. Dose reductions were reported in 20% (sunitinib) and 100 % (EVO) of pts. Conclusions: Combination of sunitinib and EVO failed to demonstrate activity in terms of tumor shrinkage as only two patients achieved response, therefore, second stage was not proceeded. While cross trial comparisons are difficult, response rate of 12% with the combination was disappointing. Concerns over toxicity arose; translational analysis are undergoing. Clinical trial information: NCT02402062.

Phonetic interactions in the bilingual production of Galician and Spanish /e/ and /o/

Aims and objectives/purpose/research questions: This study investigates the cross-linguistic phonetic interactions in the production of closed mid vowels of Galician-Spanish bilinguals in a semi-urban area in Galicia. The research questions were: (1) Do Galician-Spanish bilinguals produce /e/ and /o/ similarly in their two languages? (2) Does language dominance influence whether these sounds are produced more like Spanish or more like Galician? (3) Do age and gender influence the bilingual production of Galician and Spanish /e/ and /o/? Design/methodology/approach: Thirty Galician-Spanish bilinguals from the western coast of Galicia completed a sociolinguistic questionnaire and two reading tasks in both Galician and Spanish. Data and analysis: 4,728 vowels were acoustically analyzed and submitted to several mixed effect statistical models. Findings/conclusions: Bilinguals in this study produce distinct phonetic categories for their four Galician mid vowels, and additionally have created new phonetic categories to accommodate their L2 (Spanish) vowels, resulting in a more crowded mid-vowel phonetic space. Originality: This is the first study to examine closed mid vowel realizations in both Spanish and Galician by bilinguals who maintain a Galician four mid-vowel contrast, and to investigate their complex L1-L2 phonetic interactions. Significance/implications: This study offers new data to examine how early bilinguals organize their phonetic system(s) through cross-linguistic assimilation and dissimilation.