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This study used visual-world eye tracking to examine the effect—first observed in Chan and Vitevitch (2009)—of the phonological neighborhood clustering coefficient on the time course of lexical access in spoken word recognition. Target words from neighborhoods with relatively high clustering (i.e., neighbors of the target word are also neighbors of each other) showed a significant lag in eye fixations relative to words from less clustered neighborhoods after controlling for neighborhood density, target frequency, neighborhood frequency, and multiple phonotactic probability measures. This effect was also influenced by lexical frequency, neighborhood density, and neighborhood frequency, suggesting that neighborhood clustering influences spoken word recognition, and should be included in models of this process.

This study investigates how phonological and phonetic aspects of the native-language (L1) intonation modulate the use of tonal cues in second-language (L2) speech segmentation. Previous research suggested that prosodic learning is more difficult if the L1 and L2 intonations are phonologically similar but phonetically different (French–Korean) than if they are phonologically different (English–French/Korean) (Prosodic-Learning Interference Hypothesis; Tremblay, Broersma, Coughlin & Choi, 2016). This study provides another test of this hypothesis. Korean listeners and French-speaking and English-speaking L2 learners of Korean in Korea completed an eye-tracking experiment investigating the effects of phrase tones in Korean. All groups patterned similarly with the phrase-final tone, but, unlike Korean and French listeners, English listeners showed early benefits from the phrase-initial tone (signaling word-initial boundaries in English). Importantly, French listeners patterned like Korean listeners with both tones. The Prosodic-Learning Interference Hypothesis is refined to suggest that prosodic learning difficulties may not be persistent for immersed L2 learners.

Few studies have focused on dose-response analyses of multi-strain probiotics in the general adult population. This study aimed at comparing how a low- and high-dose of a multi-strain probiotic supplement (containing

This study investigates how the fine-grained phonetic realization of tonal cues impacts speech segmentation when the cues signal the same word boundary in the native and unfamiliar languages but do so differently. Korean listeners use the phrase-final high (H) tone and the phrase-initial low (L) tone to segment speech into words (Kim, Broersma, & Cho, 2012; Kim & Cho, 2009), but it is unclear how the alignment of the phrase-final H tone and the scaling of the phrase-initial L tone modulate their speech segmentation. Korean listeners completed three artificial-language (AL) tasks (within-subject): (a) one AL without tonal cues; (b) one AL with later-aligned phrase-final H cues (non-Korean-like); and (c) one AL with earlier-aligned phrase-final H cues (Korean-like). Three groups of Korean listeners heard (b) and (c) in three phrase-initial L scaling conditions (between-subject): high (non-Korean-like), mid (non-Korean-like), or low (Korean-like). Korean listeners’ segmentation improved as the L tone was lowered, and (b) enhanced segmentation more than (c) in the high- and mid-scaling conditions. We propose that Korean listeners tune in to low-level cues (the greater H-to-L slope in [b]) that conform to the Korean intonational grammar when the phrase-initial L tone is not canonical phonologically.

We investigate whether acoustic cue weightings are transferred from the native language to the second language [research question 1 (RQ1)], how cue weightings change with increasing second-language proficiency (RQ2), and whether individual cues are used independently or together in the second language (RQ3). Vowel reduction is a strong cue to lexical stress in English but not Dutch. Native English listeners and Dutch second-language learners of English completed a cue-weighting stress perception experiment. Participants heard sentence-final pitch-accented auditory stimuli and identified them as DEsert (initial stress) or deSSERT (final stress). The stimuli were manipulated in seven steps from initial to final stress, manipulating two dimensions at a time: vowel quality and pitch, vowel quality and duration, and pitch and duration (other dimensions neutralized). Dutch listeners relied less on vowel quality and more on pitch than English listeners, with Dutch listeners' sensitivity to vowel quality increasing with English proficiency but their sensitivity to pitch not varying with proficiency; Dutch listeners evidenced similar or weaker reliance on duration than did English listeners, and their sensitivity to duration increased with proficiency; and Dutch listeners' use of pitch and duration were positively related. These results provide general support for a cue-based transfer approach to the perception of lexical stress.

A probiotic formulation combining Lactobacillus helveticus Rosell®-52, Bifidobacterium infantis Rosell®-33, and Bifidobacterium bifidum Rosell®-71 with fructooligosaccharides, first commercialized in China, has been sold in over 28 countries since 2002. Clinical studies with this blend of strains were conducted mainly in pediatric populations, and most were published in non-English journals. This comprehensive review summarizes the clinical studies in infants and children to evaluate the efficacy of this probiotic for pediatric indications. Literature searches for pediatric studies on Biostime® or Probiokid® (non-commercial name) in 6 international and Chinese databases identified 28 studies, which were classified by indications. Twelve studies show that the probiotic significantly increases the efficacy of standard diarrhea treatment regardless of etiology, reducing the risk of unresolved diarrhea (RR 0.31 [0.23; 0.42]; p < 0.0001) by 69%. In eight studies, the probiotic enhanced immune defenses, assessed by levels of various immune competence and mucosal immunity markers (six studies), and reduced the incidence of common infections (two studies). The probiotic improved iron deficiency anemia treatment efficacy (three studies), reducing the risk of unresolved anemia by 49% (RR 0.51 [0.28; 0.92]; p = 0.0263) and significantly reducing treatment side effects by 47% (RR 0.53 [0.37; 0.77]; p = 0.0009). Other studies support further investigation into this probiotic for oral candidiasis, eczema, feeding intolerance in premature babies, or hyperbilirubinemia in newborns.

The production and perception of a second language (L2) will be affected by any differences between native language (L1) and L2 lexical stress and lexical tone. This chapter first discusses L1 effects on the perception of L2 words that differ in stress, comparing the explanatory power of phonological (stress-parameter-based) and phonetic (cue-based) approaches for L2 learners’ performance in word recognition. Equally, it discusses L1 effects on the production of stress in L2 words, from both a phonological and a phonetic perspective. The discussion then moves on to the L2 acquisition of lexical tone, focusing on differences in the way native speakers and L2 learners make use of lower-level acoustic-phonetic and higher-level linguistic information, their weighting of tonal cues (pitch height and pitch direction), and the role of contextual phonetic and prosodic information. Special attention is paid to major typological differences between L1 and L2 (non-tonal vs. tonal; level tones vs. contour tones). Finally, the efficacy of short-term auditory training in the acquisition of new tonal categories is evaluated. Throughout, the chapter addresses the influence of factors such as age of acquisition and proficiency.

This study newly investigates whether the functional weight of a prosodic cue in the native language predicts listeners’ learning and use of that cue in second-language speech segmentation. It compares English and Dutch listeners’ use of fundamental-frequency (F0) rise as a cue to word-final boundaries in French. F0 rise signals word-initial boundaries in English and Dutch, but has a weaker functional weight in English than Dutch because it is more strongly correlated with vowel quality in English than Dutch. English- and Dutch-speaking learners of French matched in French proficiency and experience, and native French listeners completed a visual-world eye-tracking experiment in French where they monitored words ending with/out an F0 rise (replication of Tremblay, Broersma, Coughlin & Choi, 2016). Dutch listeners made earlier/greater use of the F0 rise than English listeners, and in one condition they made greater use of F0 rise than French listeners, extending the cue-weighting theory to speech segmentation.

Caspase-3 activation in the limbic system and depressive-like symptoms are observed after an acute myocardial infarction (MI) and studies suggest that inflammation may play a significant role. Combined treatment with the probiotic strains Bifidobacterium longum and Lactobacillus helveticus in rats has been shown to attenuate caspase-3 activation and depressive-like behaviour together with a reduction in pro-inflammatory cytokines. The present study was designed to determine the respective contribution of these two strains on caspase-3 activity in the limbic system and on depressive-like behaviour. Sprague-Dawley rats were assigned to one of four groups: Vehicle, L. helveticus R0052, B. longum R0175 and L. salivarius HA-118, administered orally for 14 days (109CFU daily) before inducing MI by occlusion of the left anterior descending artery for 40 min followed by 14 days of reperfusion. Animals were then tested for socialisation, passive avoidance and forced swim test to assess depressive-like behaviour. At day 18 the animals were sacrificed; infarct size was estimated, plasma C-reactive protein concentration and brain caspase-3 activity were measured. Results indicated that infarct size did not vary across the different treatments. Rats treated with B. longum spent more time socializing, learned more rapidly the passive avoidance test and spent less time immobile in the forced swim test compared to the vehicle groups. Caspase-3 activity and plasma C-reactive protein concentrations were reduced in the lateral and medial amygdala as well as in the dentate gyrus of B. longum-supplemented animals. The only significant effect in the two groups receiving Lactobacilli compared to vehicle was that rats receiving L. salivarius learned more rapidly in the step-down passive avoidance test. In conclusion, most of the beneficial effects that we previously reported with the combination of two probiotic strains in our experimentation regarding post-myocardial infarction depression are related to Bifidobacterium longum.

Psychobiotics are considered among potential avenues for modulating the bidirectional communication between the gastrointestinal tract and central nervous system, defined as the microbiota-gut-brain axis (MGBA). Even though causality has not yet been established, intestinal dysbiosis has emerged as a hallmark of several diseases, including neuropsychiatric disorders (NPDs). The fact that the microbiota and central nervous system are co-developing during the first years of life has provided a paradigm suggesting a potential role of psychobiotics for earlier interventions. Studies in animal models of early-life stress (ELS) have shown that they can counteract the pervasive effects of stress during this crucial developmental period, and rescue behavioral symptoms related to anxiety and depression later in life. In humans, evidence from clinical studies on the efficacy of psychobiotics at improving mental outcomes in most NPDs remain limited, except for major depressive disorder for which more studies are available. Consequently, the beneficial effect of psychobiotics on depression-related outcomes in adults are becoming clearer. While the specific mechanisms at play remain elusive, the effect of psychobiotics are generally considered to involve the hypothalamic-pituitary-adrenal axis, intestinal permeability, and inflammation. It is anticipated that future clinical studies will explore the potential role of psychobiotics at mitigating the risk developing NPDs in vulnerable individuals or in the context of childhood adversity. However, such studies remain challenging at present in terms of design and target populations; the profound impact of stress on the proper development of the MGBA during the first year of life is becoming increasingly recognized, but the trajectories post-ELS in humans and the mechanisms by which stress affects the susceptibility to various NPDs are still ill-defined. As psychobiotics are likely to exert both shared and specific mechanisms, a better definition of target subpopulations would allow to tailor psychobiotics selection by aligning mechanistic properties with known pathophysiological mechanisms or risk factors. Here we review the available evidence from clinical and preclinical studies supporting a role for psychobiotics at ameliorating depression-related outcomes, highlighting the knowledge gaps and challenges associated with conducting longitudinal studies to address outstanding key questions in the field.

This study investigates whether second language learners’ processing of stress can be explained by the degree to which suprasegmental cues contribute to lexical identity in the native language. It focuses on Standard Mandarin, Taiwan Mandarin, and American English listeners’ processing of stress in English nonwords. In Mandarin, fundamental frequency contributes to lexical identity by signaling lexical tones, but only in Standard Mandarin does duration distinguish stressed–unstressed and stressed–stressed words. Participants completed sequence-recall tasks containing English disyllabic nonwords contrasting in stress. Experiment 1 used natural stimuli; Experiment 2 used resynthesized stimuli that isolated fundamental frequency and duration cues. Experiment 1 revealed no difference among the groups; in Experiment 2, Standard Mandarin listeners used duration more than Taiwan Mandarin listeners did. These results are interpreted within a cue-weighting theory of speech perception.

In their article, Mougeon, Hallion, Bigot, and Papen attempt to explain the similarities and differences among four varieties of Canadian French spoken outside Quebec (and New Brunswick) in the use of the restriction forms rien que, juste, seulement (que), and ne . . . que. Mougeon and colleagues focused on the French varieties spoken in Welland (Ontario), Saint-Boniface (Manitoba), Saint-Laurent (i.e., Mitchif French, Manitoba) and Bonnyville (Alberta) (see also Nadasdi & Keppie 2004). Using a variationist sociolinguistic framework, they examined the effect of linguistic and extralinguistic factors on speakers’ use of the aforementioned restriction forms, and compared their results to those reported in previous studies of the French varieties spoken in Montreal (Quebec) (Massicotte 1984, 1986; Thibault & Daveluy 1989) and in Hawkesbury, Cornwall, Northbay, and Pembroke (Ontario) (Rehner & Mougeon 1998). Based on their results, Mougeon and colleagues made hypotheses regarding linguistic convergence/divergence and raise relevant questions for future research. In this commentary, I briefly assess some of the contributions made by this research from a psycholinguistic perspective. In doing so, I raise additional questions concerning the source of the effects reported in the study.

This study investigates whether syntactic cues take precedence over distributional cues in native and non-native speech segmentation by examining native and non-native speech segmentation in potential French-liaison contexts. Native French listeners and English-speaking second-language learners of French completed a visual-world eye-tracking experiment. Half the stimuli contained the pivotal consonant /t/, a frequent word onset but infrequent liaison consonant, and half contained /z/, a frequent liaison consonant but rare word onset. In the adjective–noun condition (permitting liaison), participants heard a consonant-initial target (e.g., le petit tatoué; le fameux zélé) that was temporarily ambiguous at the segmental level with a vowel-initial competitor (e.g., le petit [t]athée; le fameux [z]élu); in the noun–adjective condition (not permitting liaison), they heard a consonant-initial target (e.g., le client tatoué; le Français zélé) that was not temporarily ambiguous with a vowel-initial competitor (e.g., le client [*t]athée; le Français [*z]élu). Growth-curve analyses revealed that syntactic context modulated both groups’ fixations (noun–adjective > adjective–noun), and pivotal consonant modulated both groups’ fixations (/t/ > /z/) only in the adjective–noun condition, with the effect of the consonant decreasing in more proficient French learners. These results suggest that syntactic cues override distributional cues in the segmentation of French words in potential liaison contexts.

This study investigated the elicited imitation task (EIT) as a tool for measuring linguistic proficiency in a second/foreign (L2) language, focusing on French. Nonnative French speakers (n = 94) and native French speakers (n = 6) completed an EIT that included 50 sentences varying in length and complexity. Three raters evaluated productions on five scales: meaning, syntax, morphology, vocabulary, and pronunciation. Participants also completed a cloze test and a language background questionnaire. Results from regression and principal component analyses showed a strong relationship between EIT performance and cloze test scores and significant relationships between EIT performance, sentence length, and learners’ knowledge of and experience with French. Ratings were internally consistent, and all test items discriminated well between lower- and higher-level learners. We argue that this EIT exhibits good validity and reliability, discriminates among French learners of different proficiencies, and is a practical tool for L2 proficiency assessment.

This study investigates whether adult second language learners’ online processing of wh-dependencies is constrained by island constraints on movement. Proficiency-matched Spanish and Korean learners of English completed a grammaticality judgment task and a stop-making-sense task designed to examine their knowledge of the relative clause island constraint and their sensitivity to this constraint in online wh-dependency formation. The results showed that both learner groups have knowledge of the island constraint in English. However, unlike the Spanish speakers, who immediately applied the constraint to prevent the formation of an ungrammatical wh-dependency, the Korean speakers showed evidence of temporarily entertaining an ungrammatical dependency. These findings suggest that the properties of the native language influence the online processing of L2 sentences.

Receptor-mediated internalization followed by trafficking and degradation of antibody-conjugates (ACs) via the endosomal-lysosomal pathway is the major mechanism for delivering molecular payloads inside target tumor cells. Although a mainstay for delivering payloads with clinically approved ACs in cancer treatment and imaging, tumor cells are often able to decrease intracellular payload concentrations and thereby reduce the effectiveness of the desired application. Thus, increasing payload intracellular accumulation has become a focus of attention for designing next-generation ACs. We developed a composite compound (ChAcNLS) that enables ACs to escape endosome entrapment and route to the nucleus resulting in the increased intracellular accumulation as an interleukin-5 receptor α-subunit (IL-5Rα)-targeted agent for muscle invasive bladder cancer (MIBC). We constructed ⁶⁴Cu-A14-ChAcNLS, ⁶⁴Cu-A14-NLS, and ⁶⁴Cu-A14 and evaluated their performance by employing mechanistic studies for endosome escape coupled to nuclear routing and determining whether this delivery system results in improved ⁶⁴Cu cellular accumulation. ACs consisting of ∼20 ChAcNLS or NLS moieties per ⁶⁴Cu-A14 were prepared in good yield, high monomer content, and maintaining high affinity for IL-5Rα. Confocal microscopy analysis demonstrated ChAcNLS mediated efficient endosome escape and nuclear localization. ⁶⁴Cu-A14-ChAcNLS increased ⁶⁴Cu cellular accumulation in HT-1376 and HT-B9 cells relative to ⁶⁴Cu-A14 and ⁶⁴Cu-A14-NLS. In addition, we tested ⁶⁴Cu-A14-ChAcNLS in vivo to evaluate its tissue distribution properties and, ultimately, tumor uptake and targeting. A model of human IL-5Rα MIBC was developed by implanting NOD/SCID mice with subcutaneous HT-1376 or HT-B9MIBC tumors, which grow containing high and low IL-5Rα-positive tumor cell densities, respectively. ACs were intravenously injected, and daily blood sampling, biodistribution at 48 and 96 h, and positron emission tomography (PET) at 24 and 48 h were performed. Region of interest (ROI) analysis was also performed on reconstructed PET images. Pharmacokinetic analysis and biodistribution studies showed that ⁶⁴Cu-A14-ChAcNLS had faster clearance rates from the blood and healthy organs relative to ⁶⁴Cu-A14. However, ⁶⁴Cu-A14-ChAcNLS maintained comparable tumor accumulation relative to ⁶⁴Cu-A14. This resulted in ⁶⁴Cu-A14-ChAcNLS having superior tumor/normal tissue ratios at both 48 and 96 h biodistribution time points. Visualization of AC distribution by PET and ROI analysis confirmed that ⁶⁴Cu-A14-ChAcNLS had improved targeting of MIBC tumor relative to ⁶⁴Cu-A14. In addition, ⁶⁴Cu-A14 modified with only NLS had poor tumor targeting. This was a result of poor tumor uptake due to extremely rapid clearance. Thus, the overall findings in this model of human IL-5Rα-positive MIBC describe an endosome escape-nuclear localization cholic-acid-linked peptide that substantially enhances AC cellular accumulation and tumor targeting. Refereed/Peer-reviewed

This study investigates whether late second/foreign language (L2) learners can rely on mechanisms similar to those of native speakers for processing morphologically complex words. Specifically, it examines whether native English speakers who have begun learning French around the onset of puberty can decompose -er (Class I) French verbs. Mid-to-high-proficiency L2 learners and native French speakers completed a masked-priming word-naming task. Latencies for morphologically related, orthographically related, and semantically related prime–target combinations were compared to latencies for identical and unrelated prime–target combinations. The results reveal the following effects: full morphological priming for both native and non-native speakers, with this effect increasing with French proficiency for L2 learners; partial orthographic priming for both groups; greater priming in the morphological condition than in the orthographic condition for both groups; and no semantic priming for either group. We conclude that L2 learners have access to similar mechanisms to those of native speakers for processing morphologically complex words.

This study investigates whether prosodically driven variants constrain lexical access by focusing on the processing of prosodically licit and illicit Korean lenis plosives and nasals. Lenis plosives are aspirated phrase-initially but voiced phrase-medially; nasals undergo nasal weakening (“denasalization”) phrase-initially but not phrase-medially. Importantly, denasalized nasals share acoustic similarities with voiced lenis plosives. Seoul Korean listeners completed four cross-modal priming experiments where primes in phrase-initial sentential position were related (experimental) (e.g., /tapal/ “bundle”) or unrelated (control) (e.g., /tʃodɛ/ “invitation”) to visual targets (e.g., 다발/tapal/). The target began with a lenis plosive (Exps. 1 and 2) or nasal (Exps. 3 and 4). The experimental prime began with a prosodically licit (Exp. 1: aspirated lenis, Exp. 3: denasalized nasal) or illicit (Exp. 2: voiced lenis, Exp. 4: nasalized nasal) variant. The results showed that experimental primes with a prosodically licit variant (Exps. 1 and 3) facilitated word recognition. For prosodically illicit variants, experimental primes with a nasalized nasal (Exp. 4) facilitated word recognition but experimental primes with a voiced plosive did not (Exp. 2). The facilitation in Exp. 4 suggests that prosodically driven variants do not constrain lexical access; the lack of facilitation in Exp. 2 is attributed to lexical competition from nasal-initial words.This study investigates whether prosodically driven variants constrain lexical access by focusing on the processing of prosodically licit and illicit Korean lenis plosives and nasals. Lenis plosives are aspirated phrase-initially but voiced phrase-medially; nasals undergo nasal weakening (“denasalization”) phrase-initially but not phrase-medially. Importantly, denasalized nasals share acoustic similarities with voiced lenis plosives. Seoul Korean listeners completed four cross-modal priming experiments where primes in phrase-initial sentential position were related (experimental) (e.g., /tapal/ “bundle”) or unrelated (control) (e.g., /tʃodɛ/ “invitation”) to visual targets (e.g., 다발/tapal/). The target began with a lenis plosive (Exps. 1 and 2) or nasal (Exps. 3 and 4). The experimental prime began with a prosodically licit (Exp. 1: aspirated lenis, Exp. 3: denasalized nasal) or illicit (Exp. 2: voiced lenis, Exp. 4: nasalized nasal) variant. The results showed that experimental primes with a prosodically...

This study investigates English listeners’ use of distributional and acoustic-phonetic cues to liaison in French. Liaison creates a misalignment of the syllable and word boundaries, but is signaled by distributional cues (/z/ is a frequent liaison but not a frequent word onset; /t/ is a frequent word onset but a less frequent liaison) and acoustic-phonetic cues (liaison consonants are 15 per cent shorter than word-initial consonants). English-speaking French learners completed a visual-world eye-tracking experiment in which they heard adjective-noun sequences where the pivotal consonant was /t/ (expected advantage for consonant-initial words) or /z/ (expected advantage for liaison-initial words). Their results were compared to those of native French speakers. Both groups showed an advantage for consonant-initial targets with /t/ but no advantage for consonant- or liaison-initial targets with /z/. Both groups’ competitor fixations were modulated by the duration of the pivotal consonant, but only the learners’ fixations to liaison-initial targets were modulated by the duration of the pivotal consonant. This suggests that English listeners use both top-down (distributional) and bottom-up (acoustic-phonetic) cues to liaison in French. Their greater reliance on acoustic-phonetic cues is hypothesized to stem in part from English, where such cues play an important role for locating word boundaries.