First-in-human clinical trial of allogeneic, platelet-derived extracellular vesicles as a potential therapeutic for delayed wound healing.

The release of growth factors, cytokines and extracellular matrix modifiers by activated platelets is an important step in the process of healthy wound healing. Extracellular vesicles (EVs) released by activated platelets carry this bioactive cargo in an enriched form, and may therefore represent a potential therapeutic for the treatment of delayed wound healing, such as chronic wounds. While EVs show great promise in regenerative medicine, their production at clinical scale remains a critical challenge and their tolerability in humans is still to be fully established. In this work, we demonstrate that Ligand-based Exosome Affinity Purification (LEAP) chromatography can successfully isolate platelet EVs (pEVs) of clinical grade from activated platelets, which retain the regenerative properties of the parent cell. LEAP-isolated pEVs display the expected biophysical features of EV populations and transport essential proteins in wound healing processes, including insulin growth factor (IGF) and transforming growth factor beta (TGF-ß). In vitro studies show that pEVs induce proliferation and migration of dermal fibroblasts and increase dermal endothelial cells' angiogenic potential, demonstrating their wound healing potential. pEV treatment activates the ERK and Akt signalling pathways within recipient cells. In a first-in-human, double-blind, placebo-controlled, phase I clinical trial of healthy volunteer adults, designed primarily to assess safety in the context of wound healing, we demonstrate that injections of LEAP-purified pEVs in formulation buffer are safe and well tolerated (Plexoval II study, ACTRN12620000944932). As a secondary objective, biological activity in the context of wound healing rate was assessed. In this cohort of healthy participants, in which the wound bed would not be expected to be deficient in the bioactive cargo that pEVs carry, all wounds healed rapidly and completely and no difference in time to wound closure of the treated and untreated wounds was observed at the single dose tested. The outcomes of this study evidence that pEVs manufactured through the LEAP process can be injected safely in humans as a potential wound healing treatment, and warrant further study in clinical trials designed expressly to assess therapeutic efficacy in patients with delayed or disrupted wound healing.

Relationship Between Cognitive Functions and Multilevel Language Processing: Data From Chinese Speakers With Aphasia and Implications.

PURPOSE: This study aims to investigate the relationship between nonverbal cognitive functions and language processing of people with aphasia (PWA) by taking a data-driven approach, as well as multiple cognitive components and multilevel linguistic perspectives. It is hypothesized that language performance is differentially associated with cognitive processing of PWA, with executive functions (EFs) playing a stronger role in language tasks with increasing linguistic complexity. METHOD: A language battery assessing word comprehension/production, sentence comprehension, and discourse production, together with a series of nonlinguistic cognitive tasks targeting simple/complex attention, short-term/working memory, or EFs, was administered to 53 Cantonese-speaking PWA. Cognitive factors extracted from principal component analysis applied to the cognitive battery served as predictors in four multiple regression analyses to predict PWA's performance at various linguistic levels. RESULTS: Two cognitive factors, representing (a) simple attention and memory and (b) EF, were extracted. The former predicted performance in word processing tasks, whereas EF significantly predicted performance in all language tasks with increasing contribution as a function of linguistic complexity. CONCLUSION: The results based on Chinese PWA provide comprehensive evidence for the view that language performance is the end product of interaction between linguistic and nonlinguistic functions and have clear implications for clinical management of PWA.

Dissociation of tone merger and congenital amusia in Hong Kong Cantonese.

While the issue of individual variation has been widely studied in second language learning or processing, it is less well understood how perceptual and musical aptitude differences can explain individual variation in native speech processing. In the current study, we make use of tone merger in Hong Kong Cantonese, an ongoing sound change that concerns the merging of tones in perception, production or both in a portion of native speakers, to examine the possible relationship between tone merger and musical and pitch abilities. Although a previous study has reported the occurrence of tone merger independently of musical training, it has not been investigated before whether tone-merging individuals, especially those merging tones in perception, would have inferior musical perception and fine-grained pitch sensitivities, given the close relationship of speech and music. To this end, we tested three groups of tone-merging individuals with various tone perception and production profiles on musical perception and pitch threshold tasks, in comparison to a group of Cantonese speakers with congenital amusia, and another group of controls without tone merger or amusia. Additionally, the amusics were compared with tone-merging individuals on the details of their tone discrimination and production profiles. The results showed a clear dissociation of tone merger and amusia, with the tone-merging individuals exhibiting intact musical and pitch abilities; on the other hand, the amusics demonstrated widespread difficulties in tone discrimination yet intact tone production, in contrast to the highly selective confusion of a specific tone pair in production or discrimination in tone-merging individuals. These findings provide the first evidence that tone merger and amusia are distinct from each other, and further suggest that the cause of tone merger may lie elsewhere rather than being driven by musical or pitch deficits. We also discussed issues arising from the current findings regarding the neural mechanisms of tone merger and amusia.

N170 reflects orthographic uniqueness point effects in English among native Japanese and Korean readers.

Orthographic uniqueness point (OUP) refers to the letter position of a word at which it is distinguishable from other lexical items in the language. Previous findings of OUP effects have been mixed and mainly demonstrated in native readers of alphabetic languages. The current study investigated whether OUP effects could be shown among non-native readers in a visual repetition detection task. The experiment tested three OUP conditions (early, mid, late) in native English readers and proficient non-native English readers whose native scripts were Japanese or Korean. Results revealed main effects of OUP on N170 amplitude, where early OUP words elicited more negative N170 and late OUP words elicited marginally less negative N170 than mean activation for both native and non-native readers. There was no indication that non-linearity or non-alphabetic nature of one's native script influenced OUP effects. Results were consistent with a parallel letter processing account in single word reading.

Functional orthographic units in Chinese character reading: Are there abstract radical identities?

Previous research has shown that the components of Chinese characters (e.g., semantic components, phonetic components, and radicals) serve as processing units in reading. One outstanding question concerns the existence of amodal orthographic representations that unify multiple, form-specific character components, similar to the abstract letter identities (ALIs) that unify case-specific letter forms (A/a) in Roman script. Although Chinese does not have case, a subset of semantic radicals have multiple forms (e.g., - are both "water" radicals), allowing for a test of the existence of Abstract Radical Identities (ARIs) that unify the multiple forms. In Experiment 1, a visual same-different judgement task was used to detect the presence of ARI representations. Evidence for ARIs was provided by the finding that radical pairs with different forms but the same radical identity were judged to be visually different more slowly than matched pairs of different forms with different radical identities. In Experiment 2, we evaluated ARI effects in real character reading. A lexical decision priming task compared prime-target character pairs containing radicals with the same identity but different forms (e.g., -) with matched prime-target character pairs with unrelated radicals (e.g., -). Inhibitory priming was observed only in the same-identity radical condition compared with the unrelated condition. These combined results provide, for the first time, evidence of format-free representations of orthographic units in Chinese characters-abstract radical identities (ARIs).

Top-down and bottom-up mechanisms as reflected by beta and gamma oscillations in speech perception: An individual-difference approach.

Recent neurophysiological studies have proposed distinct roles of ß and γ oscillations in implementing top-down and bottom-up processes. The present study aims to test this hypothesis in the domain of speech perception. We examined ß and γ oscillations elicited to a tone contrast in a passive oddball paradigm, and their relationships with discrimination sensitivity d' and RT from two groups of healthy adults who showed high and low discrimination sensitivity to the contrast. The low-sensitivity group showed a significant reduction in ß, which was further related to d'. Individual differences in RT were related to different frequency bands in the two groups, with a RT-ß correlation in the low-sensitivity group, and a RT-γ relation in the high-sensitivity group. Based on these findings, we suggest that ß, implicated in top-down processing, reflects individual differences in phonological representations, and that γ, involved in bottom-up processing, reflects individual differences in acoustic encoding.

Interactions of age of acquisition and lexical frequency effects with phonological regularity: An ERP study.

Across languages, lexical frequency and age of acquisition (AoA) are important predictors of word reading that are naturally correlated, and both variables have been shown to interact with phonological regularity. Previous behavioral findings in Chinese have shown stronger regularity effects in low frequency relative to high frequency characters. Meanwhile, the arbitrary mapping hypothesis predicts stronger interference effects in late-acquired irregular words. This study examined the neural bases of these phenomena in Chinese using a delayed naming task with 480 single characters. Single-trial ERP analyses were conducted to contrast the interactions of frequency or AoA effects with phonological regularity, while controlling for the other factor. Results showed differential and significant effects of AoA and frequency at the N400 and late positive component (LPC), respectively, indicating their independence. ERP interaction patterns of frequency and regularity in Chinese were observed for the first time in the LPC time window and suggested semantic interference from sublexical units during character reading. Interaction of AoA and regularity at the N400 could be explained by the semantic hypothesis but appeared inconsistent with the arbitrary mapping hypothesis.

Use of co-verbal gestures during word-finding difficulty among Cantonese speakers with fluent aphasia and unimpaired controls.

BACKGROUND: Co-verbal gestures refer to hand or arm movements made during speaking. Spoken language and gestures have been shown to be tightly integrated in human communication. AIMS: The present study investigated whether co-verbal gesture use was associated with lexical retrieval in connected speech in unimpaired speakers and persons with aphasia (PWA). METHODS & PROCEDURES: Narrative samples of 58 fluent PWA and 58 control speakers were extracted from Cantonese AphasiaBank. Based on the indicators of word-finding difficulty (WFD) in connected speech adapted from previous research, and a gesture annotation system with independent coding of gesture forms and functions, all WFD instances were identified. The presence and type of gestures accompanying each incident of WFD were then annotated. Finally, whether the use of gesture was accompanied by resolution of WFD, i.e., the corresponding target word could be retrieved, was examined. OUTCOMES & RESULTS: Employment of co-verbal gesture did not seem to be related to the success of word retrieval. PWA's naming ability at single-word level and their overall language ability (as reflected by the aphasia quotient of the Cantonese version of the Western Aphasia Battery) were found to be the two strongest predictors of success rate of resolving WFD. CONCLUSIONS: The Lexical Retrieval Hypothesis highlighting the facilitative functions of iconic and metaphoric gestures in lexical retrieval was not supported. Challenges in conducting research related to WFD, and the clinical implications in gesture-based language intervention for PWA were discussed.

Cantonese AphasiaBank: An annotated database of spoken discourse and co-verbal gestures by healthy and language-impaired native Cantonese speakers.

This article reports the construction of a multimodal annotated database of spoken discourse and co-verbal gestures by native healthy speakers of Cantonese and individuals with language impairment: the Cantonese AphasiaBank. This corpus was established as a foundation for aphasiologists and clinicians to use in designing and conducting research investigations into theoretical and clinical issues related to acquired language disorders in Chinese. Details in terms of the purpose, structure, and levels of annotation of the database (containing part-of-speech-annotated orthographic transcripts with Romanization and the corresponding videos) are described. The discussion presents the challenges of building a spoken database of a language that is not linguistically well-researched and that does not have a standardized written form for many of its lexical items, as well as presenting how these issues were addressed. Most importantly, the article highlights the potential of Cantonese AphasiaBank as a powerful research tool for linguists and psycholinguists.

Impact of characteristics of L1 literacy experience on picture processing: ERP data from trilingual non-native Chinese and English readers.

Previous studies involving ex-illiterate and young readers of alphabetic scripts have shown that processing of non-verbal visual stimuli may be affected by literacy, which is attributable to intensive perceptual training during reading acquisition. This study examined whether the characteristics of one's native writing system, with respect to visual complexity and overall shape of orthographic unit, would influence the processing of pictured objects using event-related potential (ERP) with linear mixed-effects modeling. Kanji and Hangul constitute an interesting contrast as they differ in visual complexity but are similar in orthographic shape. Neural responses to pictures were analyzed in N170 and N400 reflecting ease of recognition and access to semantic representation, respectively. Trilingual speakers with Japanese or Korean as L1, who learned to read Chinese and English as non-native languages, as well as native Chinese and native English readers participated in a repetition detection task in which mixed blocks of pictures and words (Chinese or English) were presented. The overall results showed bilaterally distributed N170 and N400, and group differences in the N400 were confined to the anterior region. More importantly, Japanese readers exhibited more negative N170 and less negative N400 than Korean participants regardless of language context. The present findings have provided insights into the possible impact of reading acquisition on non-linguistic visual processing, and suggest that one's early experience of a visually complex orthography has positive transfer to processing of line drawings in terms of more efficient visual recognition and semantic access.

Induced gamma oscillations index individual differences in speech sound perception and production.

Auditory neuroscience has provided strong evidence that neural oscillations synchronize to the rhythm of speech stimuli, and oscillations at different frequencies have been linked to processing of different language structures. The present study aims to examine how these ubiquitous neurophysiological attributes may inform us about the brain processes that underpin individual differences in speech perception and production, which in turn elucidate the specific functions of neural oscillations in the domain of speech processing. To this end, we recorded electrophysiological responses to a lexical tone contrast in a passive auditory oddball paradigm from two groups of healthy tone-language speakers who were equal in perceptual discriminability but differed in response latency and production distinctiveness of the tone contrast. Time-frequency analysis was applied to the EEG data, and decomposed into theta (4-7 Hz), beta (12-30 Hz), and gamma (30-50 Hz) frequency bands. Results show that listeners with longer discrimination RT and less distinctive production showed significantly higher induced (non-phase-locked) gamma during tone processing. Moreover, among speakers with less distinctive production, individual differences in induced gamma were significantly correlated with discrimination latency and production distinction. Based on the present findings, we propose that differences in gamma oscillations reflect differential sensory/perceptual computations during acoustic encoding, impacting the quality of perceptual representations, which further mediates individual differences in speech perception and production.

Emulsifying properties of ruptured microalgae cells: Barriers to lipid extraction or promising biosurfactants?

A systematic investigation of the emulsifying properties of ruptured algae cells was performed for the first time. The slurry of ruptured algae cells was separated into different biomass fractions, namely the cell debris, the delipidated debris, the serum, and the lipid. The interfacial interactions of these biomass fractions with a nonpolar solvent (e.g. hexane or hexadecane) were characterized using pendant drop tensiometry and interfacial shear rheology. The stability of the different emulsions (formed by the different biomass fractions) was tested using analytical centrifugation. The extracted lipid was an excellent surfactant that reduced the interfacial tension, however, it was not effective at stabilizing the emulsions. The protein-rich serum produced a strong interfacial film that stabilized the emulsions against coalescence during centrifugation. The cell debris stabilized the emulsions to a lesser extent by adsorbing to the droplet surface, presumably via interactions with hydrophobic extracellular polymeric substances (EPS). However, neither the serum nor the cell debris were very effective surfactants, and required the presence of the lipid fraction to produce small emulsion droplets. When present together, the components exhibited competitive interfacial adsorption, which influenced emulsion stability. In particular, the interruption of the protein film by the presence of lipid or cell debris reduced the stability of the emulsions. This study provides a new mechanistic understanding of emulsification during wet lipid extraction from microalgae that will be useful for determining strategies to improve solvent recovery. The results also suggest potential for developing effective bioemulsifiers or biosurfactants from fractionated microalgae biomass for commercial application.

Conversion and recovery of saponifiable lipids from microalgae using a nonpolar solvent via lipase-assisted extraction.

A single-step method for transesterifying and recovering lipids in concentrated slurries (ca 20% w/w solids) of ruptured microalgae is presented. A soluble Rhizomucor miehei lipase (RML) was used to directly transesterify the lipids in the marine microalgae Nannochloropsis salina. This allowed both triglycerides (TAG) and polar saponifiable lipids to be recovered as fatty acid methyl esters (FAME) using a nonpolar solvent (hexane). Up to 90 wt% of the total saponifiable lipids (SL) were converted to FAME within 24 h, approximately 75% of which was recovered in the hexane by centrifugation. Two pathways for the conversion and recovery of polar lipids were identified. The water in the slurry buffered against potential lipase inhibition by methanol, but necessitated a high methanol dose for maximal FAME conversion. Nonetheless the method enables the recovery of polar lipids as FAME while avoiding the need for both drying of the biomass and a downstream transesterification step.

Measuring discourse coherence in anomic aphasia using Rhetorical Structure Theory.

PURPOSE: The existing body of work regarding discourse coherence in aphasia has provided mixed results, leaving the question of coherence being impaired or intact as a result of brain injury unanswered. In this study, discourse coherence in non-brain-damaged (NBD) speakers and speakers with anomic aphasia was investigated quantitatively and qualitatively. METHOD: Fifteen native speakers of Cantonese with anomic aphasia and 15 NBD participants produced 60 language samples. Elicitation tasks included story-telling induced by a picture series and a procedural description. The samples were annotated for discourse structure in the framework of Rhetorical Structure Theory (RST) in order to analyse a number of structural parameters. After that 20 naïve listeners rated coherence of each sample. RESULT: Disordered discourse was rated as significantly less coherent. The NBD group demonstrated a higher production fluency than the participants with aphasia and used a richer set of semantic relations to create discourse, particularly in the description of settings, expression of causality, and extent of elaboration. People with aphasia also tended to omit essential information content. CONCLUSION: Reduced essential information content, lower degree of elaboration, and a larger amount of structural disruptions may have contributed to the reduced overall discourse coherence in speakers with anomic aphasia.

An analysis of topics and vocabulary in Chinese oral narratives by normal speakers and speakers with fluent aphasia.

This study analysed the topic and vocabulary of Chinese speakers based on language samples of personal recounts in a large spoken Chinese database recently made available in the public domain, i.e. Cantonese AphasiaBank ( http://www.speech.hku.hk/caphbank/search/ ). The goal of the analysis is to offer clinicians a rich source for selecting ecologically valid training materials for rehabilitating Chinese-speaking people with aphasia (PWA) in the design and planning of culturally and linguistically appropriate treatments. Discourse production of 65 Chinese-speaking PWA of fluent types (henceforth, PWFA) and their non-aphasic controls narrating an important event in their life were extracted from Cantonese AphasiaBank. Analyses of topics and vocabularies in terms of part-of-speech, word frequency, lexical semantics, and diversity were conducted. There was significant overlap in topics between the two groups. While the vocabulary was larger for controls than that of PWFA as expected, they were similar in distribution across parts-of-speech, frequency of occurrence, and the ratio of concrete to abstract items in major open word classes. Moreover, proportionately more different verbs than nouns were employed at the individual level for both speaker groups. The findings provide important implications for guiding directions of aphasia rehabilitation not only of fluent but also non-fluent Chinese aphasic speakers.

Predictive factors for publication of abstracts at the Royal Australasian College of Surgeons Annual Scientific Congress.

BACKGROUND: A key metric of the research quality of medical conferences is the publication rate of abstracts. The study objective was to determine the publication rate of abstracts presented at the Royal Australasian College of Surgeons Annual Scientific Congress (RACS ASC) and to examine for any predictive factors associated with publication. METHODS: Abstracts presented at the RACS ASC from 2011 to 2013 were analysed. Abstract characteristics such as presentation format, study type, study design, study site, cohort size and author origin were recorded. Abstracts published were identified by a PubMed search using a strict algorithm. Univariate and multivariable logistic regressions were used to analyse for predictive factors of publication. RESULTS: Overall, 1438 abstracts were presented and 423 abstracts (29%) were published. The median time to publication was 15.2 months (interquartile range: 8-26) with 110 in Australasian journals (26%). The median number of citations for published abstracts was 6 (interquartile range: 2-16). After multivariable analysis, publication was significantly associated with prospective study design (odds ratio (OR) = 1.34, P = 0.02), multicentre study site (OR = 1.43, P = 0.02), cohort size ≥100 (OR = 2.00, P < 0.001) and New Zealand author origin (OR = 1.50, P = 0.01). CONCLUSION: Our study demonstrates that less than one-third of abstracts presented at the RACS ASC are subsequently published in a peer-reviewed journal. Factors significantly associated with journal publication include prospective studies, multicentre study, a larger cohort size and New Zealand author origin. Advances in surgery may progress from the preliminary findings of conference abstracts. However only after the rigorous peer review offered by journal publication should changes in decision-making of patient care occur.

A Comparison of Coverbal Gesture Use in Oral Discourse Among Speakers With Fluent and Nonfluent Aphasia.

Purpose: Coverbal gesture use, which is affected by the presence and degree of aphasia, can be culturally specific. The purpose of this study was to compare gesture use among Cantonese-speaking individuals: 23 neurologically healthy speakers, 23 speakers with fluent aphasia, and 21 speakers with nonfluent aphasia. Method: Multimedia data of discourse samples from these speakers were extracted from the Cantonese AphasiaBank. Gestures were independently annotated on their forms and functions to determine how gesturing rate and distribution of gestures differed across speaker groups. A multiple regression was conducted to determine the most predictive variable(s) for gesture-to-word ratio. Results: Although speakers with nonfluent aphasia gestured most frequently, the rate of gesture use in counterparts with fluent aphasia did not differ significantly from controls. Different patterns of gesture functions in the 3 speaker groups revealed that gesture plays a minor role in lexical retrieval whereas its role in enhancing communication dominates among the speakers with aphasia. The percentages of complete sentences and dysfluency strongly predicted the gesturing rate in aphasia. Conclusions: The current results supported the sketch model of language-gesture association. The relationship between gesture production and linguistic abilities and clinical implications for gesture-based language intervention for speakers with aphasia are also discussed.

A Quantitative Study of Right Dislocation in Cantonese Spoken Discourse.

Right Dislocation (RD) has been suggested to be a focus marking device carrying an affective function motivated by limited planning time in conversation. The current study investigated the effects of genre type, planning load and affective function on the use of RD in Cantonese monologues. Discourse data were extracted from a recently developed corpus of oral narratives in Cantonese Chinese containing language samples from 144 native Cantonese speakers evenly distributed in age, education levels and gender. Three genre types representing different structures, styles and degrees of topic familiarity were chosen for an RD analysis: procedural description, story-telling and recount of personal event. The results revealed that genre types and planning load influenced the rate of RD occurrence. (1) Specifically, the lowest proportion of RD occurred in procedural description, assumed to be the most structured genre; whereas the highest rate was found in personal event recount, considered to be the most stylized and less structured genre. (2) The highest proportion of RD appeared near the end of a narrative, where heavier cognitive load is demanded compared with the beginning of a narrative; moreover, RD also tended to co-occur with disfluency. (3) There was a high percentage of RD tokens in the personal event recount for expressing explicit emotions; and (4) a lower rate of occurrence of RD was found in monologues than previous studies based on conversations. The overall findings suggest that the use of RD is sensitive to genre structure and style, as well as planning load effects.

Cognitive basis of individual differences in speech perception, production and representations: The role of domain general attentional switching.

This study investigated whether individual differences in cognitive functions, attentional abilities in particular, were associated with individual differences in the quality of phonological representations, resulting in variability in speech perception and production. To do so, we took advantage of a tone merging phenomenon in Cantonese, and identified three groups of typically developed speakers who could differentiate the two rising tones (high and low rising) in both perception and production [+Per+Pro], only in perception [+Per-Pro], or in neither modalities [-Per-Pro]. Perception and production were reflected, respectively, by discrimination sensitivity d' and acoustic measures of pitch offset and rise time differences. Components of event-related potential (ERP)-the mismatch negativity (MMN) and the ERPs to amplitude rise time-were taken to reflect the representations of the acoustic cues of tones. Components of attention and working memory in the auditory and visual modalities were assessed with published test batteries. The results show that individual differences in both perception and production are linked to how listeners encode and represent the acoustic cues (pitch contour and rise time) as reflected by ERPs. The present study has advanced our knowledge from previous work by integrating measures of perception, production, attention, and those reflecting quality of representation, to offer a comprehensive account for the underlying cognitive factors of individual differences in speech processing. Particularly, it is proposed that domain-general attentional switching affects the quality of perceptual representations of the acoustic cues, giving rise to individual differences in perception and production.

Individual differences in processing pitch contour and rise time in adults: A behavioral and electrophysiological study of Cantonese tone merging.

One way to understand the relationship between speech perception and production is to examine cases where the two dissociate. This study investigates the hypothesis that perceptual acuity reflected in event-related potentials (ERPs) to rise time of sound amplitude envelope and pitch contour [reflected in the mismatch negativity (MMN)] may associate with individual differences in production among speakers with otherwise comparable perceptual abilities. To test this hypothesis, advantage was taken of an on-going sound change-tone merging in Cantonese, and compared the ERPs between two groups of typically developed native speakers who could discriminate the high rising and low rising tones with equivalent accuracy but differed in the distinctiveness of their production of these tones. Using a passive oddball paradigm, early positive-going EEG components to rise time and MMN to pitch contour were elicited during perception of the two tones. Significant group differences were found in neural responses to rise time rather than pitch contour. More importantly, individual differences in efficiency of tone discrimination in response latency and magnitude of neural responses to rise time were correlated with acoustic measures of F0 offset and rise time differences in productions of the two rising tones.