Linguistic features of stuttering during spontaneous speech.

PURPOSE: Previous work shows that linguistic features (e.g., word length, word frequency) impact the predictability of stuttering events. Most of this work has been conducted using reading tasks. Our study examined how linguistic features impact the predictability of stuttering events during spontaneous speech. METHODS: The data were sourced from the FluencyBank database and consisted of interviews with 35 adult stutterers (27,009 words). Three logistic regression mixed models were fit as the primary analyses: one model with four features (i.e., initial phoneme, grammatical function, word length, and word position within a sentence), a second model with six features (i.e., the features from the previous model plus word frequency and neighborhood density), and a third model with nine features (i.e., the features from the previous model plus bigram frequency, word concreteness, and typical age of word acquisition). We compared our models using the Area Under the Curve statistic. RESULTS: The four-feature model revealed that initial phoneme, grammatical function, and word length were predictive of stuttering events. The six-feature model revealed that initial phoneme, word length, word frequency, and neighborhood density were predictive of stuttering events. The nine-feature model was not more predictive than the six-feature model. CONCLUSION: Linguistic features that were previously found to be predictive of stuttering during reading were predictive of stuttering during spontaneous speech. The results indicate the influence of linguistic processes on the predictability of stuttering events such that words associated with increased planning demands (e.g., longer words, low frequency words) were more likely to be stuttered.

Reduced duration of stuttering-like disfluencies and consistent anticipatory slowing during an adaptation task.

PURPOSE: The adaptation effect in stuttering, traditionally described as the reduction of stuttering moments over repeated readings, provides a context to investigate fluency facilitation as well as a relatively controlled means of comparing fluent speech in the immediate vicinity of words that were stuttered versus fluently produced. Acoustic studies have documented decreased duration of fluent speech during adaptation but rarely address changes in disfluencies or the speech preceding or following the disfluencies. This study addresses this gap in the research by documenting frequency and duration changes in both fluent and stuttered syllables. METHOD: Fifteen people who stutter read passages aloud five times in succession. Frequency and duration of fluent syllables, pauses, stuttering-like disfluencies (SLDs) and other disfluencies (ODs) were compared across the five readings. In addition, durations for syllables before and after pauses and SLDs were compared to determine if there were anticipation or carryover effects of SLDs on surrounding syllables. RESULTS: Durations measured for more than 22 000 fluent syllables, 1531 pauses, 128 ODs and 1752 SLDs. For most of the 15 participants, significant decreases in both frequency and duration of SLDs over the five readings were observed. In addition, lengthening of fluent syllables immediately preceding the disfluent syllables was observed: this pre-SLD lengthening did not change over the five readings. CONCLUSIONS: Decreased duration of SLDs across readings supports the motor practice hypothesis, which assumes that successive reading of the same text increases the efficiency of the speech motor plans resulting in less stuttering and decreased durations of the stuttering that persists. Pre-SLD lengthening merits further study, because it informs our knowledge of the time course of stuttered events and may be associated with conscious or unconscious anticipation of upcoming SLDs that does not decrease with motor practice. WHAT THIS PAPER ADDS: What is already known on this subject The frequency of stuttering-like disfluencies (SLDs) can be reduced using a variety of fluency-enhancing strategies. For example, the adaptation effect, in which a reduction of stuttered events occurs over repeated readings of the same material, has been widely studied. Previous studies have shown that durations of fluent syllables decrease during adaptation, supporting the hypothesis that repeated practice of the motor plan leads to increased fluency. However, temporal changes in disfluent syllables and syllables preceding and following SLDs have rarely been studied, so our understanding of the effect of motor practice on stuttering reduction is incomplete. What this study adds This study has two significant findings. First, stuttered disfluencies that persisted after the initial reading of the adaptation task tended to become shorter in duration. Fluently produced syllables and those that were stuttered, both of which are speech events related to motor control of articulators, were affected in a similar manner by the motor practice associated with adaptation. Second, lengthening of fluent syllables immediately preceding stuttered syllables was observed. This pre-stuttering lengthening, however, did not decrease in duration over the five readings: the mechanism that drives this anticipatory behaviour is not affected by repeated practice. What are the clinical implications of this work? People who stutter have neural differences that lead to speech motor planning and/or execution that is less efficient than that of typical speakers. The finding that stuttering is reduced and that persisting SLDs become shorter in duration over repeated readings provides evidence that motor practice can influence the manifestation of stuttering by temporarily making those specific motor plans more efficient. This may inform treatments for stuttering. The observation that fluent syllables immediately before SLDs were lengthened, and that this lengthening was not influenced by repeated practice, extends our understanding of the time course of stuttering events and may be useful in understanding anticipation and listener reactions to stuttering.

Articulation Rate, Pauses, and Disfluencies in Professional Fighters: Potential Speech Biomarkers for Repetitive Head Injury.

OBJECTIVE: As part of a larger study dedicated to identifying speech and language biomarkers of neurological decline associated with repetitive head injury (RHI) in professional boxers and mixed martial artists (MMAs), we examined articulation rate, pausing, and disfluency in passages read aloud by participants in the Professional Athletes Brain Health Study. SETTING: A large outpatient medical center specializing in neurological care. PARTICIPANTS, DESIGN, AND MAIN MEASURES: Passages read aloud by 60 boxers, 40 MMAs, and 55 controls were acoustically analyzed to determine articulation rate (the number of syllables produced per second), number and duration of pauses, and number and duration of disfluencies in this observational study. RESULTS: Both boxers and MMAs differed from controls in articulation rate, producing syllables at a slower rate than controls by nearly half a syllable per second on average. Boxers produced significantly more pauses and disfluencies in passages read aloud than MMAs and controls. CONCLUSIONS: Slower articulation rate in both boxers and MMA fighters compared with individuals with no history of RHI and the increased occurrence of pauses and disfluencies in the speech of boxers suggest changes in speech motor behavior that may relate to RHI. These speech characteristics can be measured in everyday speaking conditions and by automatic recognition systems, so they have the potential to serve as effective, noninvasive clinical indicators for RHI-associated neurological decline.

Preoperative leukopenia does not affect outcomes in cancer patients undergoing elective and emergent abdominal surgery: A brief report.

BACKGROUND: Leukopenic patients have historically been considered poor surgical candidates due to a perceived increase in operative morbidity and mortality. METHODS: Retrospective cohort study using the NSQIP database to identify adult patients who received chemotherapy for malignancy within 30-days prior to elective or emergent abdominal surgery between 2008 and 2011. Leukopenia was defined as < 4000 WBC/mm3 within 2-days prior to surgery. Multiple logistic regression assessed if leukopenia was associated with morbidity and mortality. RESULTS: Of the 4369 patients included, 20.2% had preoperative leukopenia. Emergency cases comprised 36.2% of cases. Overall 30-day mortality was 12.2% and 30-day composite morbidity was 29.8%. After controlling for significant confounders, including emergency status, leukopenia was not significantly associated with either postoperative mortality (p = 0.14) or morbidity (p = 0.17). CONCLUSIONS: Our study suggests that in cancer patients undergoing chemotherapy, leukopenia is not associated with morbidity or mortality and should not influence operative planning in either the elective or emergent setting.

Service Provision for Children Who Are Hard of Hearing at Preschool and Elementary School Ages.

Purpose: To characterize preschool and school services for children who are hard of hearing (CHH), we described service setting, amount, and configuration and analyzed the relationship between service receipt and student hearing levels and language scores. Characteristics of professionals providing services were described and then used to predict level of comfort with skills supporting listening and spoken language. The amount of provider communication with children's audiologists was also investigated. Method: Participants included parents of CHH (preschool n = 174; school n = 155) and professionals (preschool n = 133; school n = 104) who completed interviews and questionnaires as part of a longitudinal study. Children's hearing, speech, and language data were collected from annual testing and analyzed in relation to service data. Results: A majority (81%) of preschool-age CHH received services. Children were more likely to be in a preschool for children who are deaf or hard of hearing (CDHH) or exceptional children than a general education preschool. By elementary school, 70% received services, nearly all in general education settings. Sessions averaged twice a week for a total of approximately 90 min. Children who no longer received services performed significantly better on speech/language measures than those who received services, regardless of service setting. Professionals were primarily speech-language pathologists (SLPs) and teachers of CDHH. SLPs reported significantly less comfort with skills involving auditory development and hearing technologies and less frequent communication with the child's audiologists than teachers of CDHH. Overall communication with audiologists was more frequent in the preschool years. Conclusions: As preschool-age CHH transition into school, the majority continue to qualify for services. Congruent with national trends, school-age CHH in the Outcomes of Children with Hearing Loss study were most often in general education settings. Without specialized preprofessional or postgraduate training, SLPs and teachers of CDHH did not report comfort with all the skills critical to developing listening and spoken language. This finding supports the need for increased implementation of interprofessional practice among SLPs and teachers of CDHH, as well as audiologists, to best meet the needs unique to this population.

Evaluation of Rhodiola crenulata on growth and metabolism of NB-1691, an MYCN-amplified neuroblastoma cell line.

Outcomes of children with high grade neuroblastoma remain poor despite multi-agent chemotherapy regimens. Rhodiola crenulata extracts display anti-neoplastic properties against several cancers including breast cancer, melanoma, and glioblastoma. In this study, we evaluated the anti-neoplastic potential of Rhodiola crenulata extracts on human neuroblastoma cells. Through this work, cell viability and proliferation were evaluated following treatments with ethanol (vehicle control) or Rhodiola crenulata extract in neuroblastoma, NB-1691 or SK-N-AS cells, in vitro. HIF-1 transcriptional activity was evaluated using a dual luciferase assay. Quantitative real-time polymerase chain reaction was utilized to assess the expression of HIF-1 targets. Selected metabolic intermediates were evaluated for their ability to rescue cells from Rhodiola crenulata extract-induced death. Lactate dehydrogenase, pyruvate kinase, and pyruvate dehydrogenase activities and NAD+/NADH levels were assayed in vehicle and Rhodiola crenulata extract-treated cells. The effects of Rhodiola crenulata extracts on metabolism were assessed by respirometry and metabolic phenotyping/fingerprinting. Our results revealed striking cytotoxic effects upon Rhodiola crenulata extract treatment, especially prominent in NB-1691 cells. As a greater response was observed in NB-1691 cells therefore it was used for remaining experiments. Upon Rhodiola crenulata extract treatment, HIF-1 transcriptional activity was increased. This increase in activity correlated with changes in HIF-1 targets involved in cellular metabolism. Serendipitously, we observed that addition of pyruvate protected against the cytotoxic effects of Rhodiola crenulata extracts. Therefore, we focused on the metabolic effects of Rhodiola crenulata extracts on NB-1691 cells. We observed that while the activities of pyruvate kinase and pyruvate dehydrogenase activities were increased, the activity of lactate dehydrogenase activity was decreased upon Rhodiola crenulata extract treatment. We also noted a decline in the total NAD pool following Rhodiola crenulata extract treatment. This correlated with decreased cellular respiration and suppressed utilization of carbon substrates. Through this work, we observed significant cytotoxic effects of Rhodiola crenulata extract treatment upon treatment on NB-1691 cells, a human neuroblastoma cell line with MYCN amplification. Our studies suggest that these cytotoxic effects could be secondary to metabolic effect induced by treatment with Rhodiola crenulata extract.

Developmental Stuttering in Children Who Are Hard of Hearing.

Purpose: A number of studies with large sample sizes have reported lower prevalence of stuttering in children with significant hearing loss compared to children without hearing loss. This study used a parent questionnaire to investigate the characteristics of stuttering (e.g., incidence, prevalence, and age of onset) in children who are hard of hearing (CHH). Method: Three hundred three parents of CHH who participated in the Outcomes of Children With Hearing Loss study (Moeller & Tomblin, 2015) were sent questionnaires asking about their child's history of stuttering. Results: One hundred ninety-four parents of CHH responded to the survey. Thirty-three CHH were reported to have stuttered at one point in time (an incidence of 17.01%), and 10 children were still stuttering at the time of survey submission (a prevalence of 5.15%). Compared to estimates in the general population, this sample displayed a significantly higher incidence and prevalence. The age of onset, recovery rate, and other characteristics were similar to hearing children. Conclusions: Based on this sample, mild to moderately severe hearing loss does not appear to be a protective factor for stuttering in the preschool years. In fact, the incidence and prevalence of stuttering may be higher in this population compared to the general population. Despite the significant speech and language needs that children with mild to moderately severe hearing loss may have, speech-language pathologists should appropriately prioritize stuttering treatment as they would in the hearing population. Supplemental Material: https://doi.org/10.23641/asha.5397154.

Individual-specific variation in the respiratory activities of HMECs and their bioenergetic response to IGF1 and TNFα.

Metabolic reprograming is a hallmark of cancer cells. However, the roles of pre-existing differences in normal cells metabolism toward cancer risk is not known. In order to assess pre-existing variations in normal cell metabolism, we have quantified the inter-individual variation in oxidative metabolism of normal primary human mammary epithelial cells (HMECs). We then assessed their response to selected cytokines such as insulin growth factor 1 (IGF1) and tumor necrosis factor alpha (TNFα), which are associated with breast cancer risk. Specifically, we compared the oxidative metabolism of HMECs obtained from women with breast cancer and without cancer. Our data show considerable inter-individual variation in respiratory activities of HMECs from different women. A bioenergetic parameter called pyruvate-stimulated respiration (PySR) was identified as a key distinguishing feature of HMECs from women with breast cancer and without cancer. Samples showing PySR over 20% of basal respiration rate were considered PySR+ve and the rest as PySR-ve . By this criterion, HMECs from tumor-affected breasts (AB) and non-tumor affected breasts (NAB) of cancer patients were mostly PySR-ve (88% and 89%, respectively), while HMECs from non-cancer patients were mostly PySR+ve (57%). This suggests that PySR-ve/+ve phenotypes are individual-specific and are not caused by field effects due to the presence of tumor. The effects of IGF1 and TNFα treatments on HMECs revealed that both suppressed respiration and extracellular acidification. In addition, IGF1 altered PySR-ve/+ve phenotypes. These results reveal individual-specific differences in pyruvate metabolism of normal breast epithelial cells and its association with breast cancer risk.

Evaluation of PolyMPC-Dox Prodrugs in a Human Ovarian Tumor Model.

A polymer prodrug, composed of doxorubicin (Dox) conjugated covalently to poly(methacryloyloxyethyl phosphorylcholine) (polyMPC), was evaluated for the treatment of human ovarian tumors in animals. PolyMPC-Dox prodrugs were prepared using facile conjugation chemistry to yield conjugates soluble in water and injectable saline, with a Dox loading of ∼19 weight percent. Toxicity evaluation showed that polyMPC was well-tolerated in mice at doses up to 800 mg/kg, confirming the biocompatibility of the polymer carrier at a high concentration. Additionally, the polyMPC-Dox prodrug was well-tolerated in animals at a Dox equivalent dose of 10 mg/kg, greater than twice the maximum tolerated dose of free Dox (∼4 mg/kg) in the same mouse strain. In a human ovarian tumor model (SKOV-3), polyMPC-Dox accumulated in tumors at twice the level of free Dox, with no additional off-target organ uptake, a result of improved pharmacokinetics afforded by the prodrug and passive targeting attributed to an enhanced permeability and retention effect. When administered to human ovarian tumor-bearing mice using a recurring dosing regimen comparable to that used clinically, polyMPC-Dox significantly retarded tumor growth relative to treatment with free Dox. Moreover, animals treated with multiple doses of polyMPC-Dox (eight total doses) exhibited enhanced survival, with a notably reduced incidence of toxicity or adverse events relative to mice treated with free Dox. These in vivo results demonstrate advantages of treating human ovarian tumors with polyMPC-Dox, including reduced systemic toxicity, improved drug accumulation in tumors, and enhanced therapeutic efficacy.

Factors Affecting Early Services for Children Who Are Hard of Hearing.

PURPOSE: To describe factors affecting early intervention (EI) for children who are hard of hearing, we analyzed (a) service setting(s) and the relationship of setting to families' frequency of participation, and (b) provider preparation, caseload composition, and experience in relation to comfort with skills that support spoken language for children who are deaf and hard of hearing (CDHH). METHOD: Participants included 122 EI professionals who completed an online questionnaire annually and 131 parents who participated in annual telephone interviews. RESULTS: Most families received EI in the home. Family participation in this setting was significantly higher than in services provided elsewhere. EI professionals were primarily teachers of CDHH or speech-language pathologists. Caseload composition was correlated moderately to strongly with most provider comfort levels. Level of preparation to support spoken language weakly to moderately correlated with provider comfort with 18 specific skills. CONCLUSIONS: Results suggest family involvement is highest when EI is home-based, which supports the need for EI in the home whenever possible. Access to hands-on experience with this population, reflected in a high percentage of CDHH on providers' current caseloads, contributed to professional comfort. Specialized preparation made a modest contribution to comfort level.

Antineoplastic effects of Rhodiola crenulata treatment on B16-F10 melanoma.

Melanoma is an aggressive form of skin cancer with limited treatment options for advanced stage disease. Early detection and wide surgical excision remain the initial mode of treatment for primary tumors thus preventing metastases and leading to improved prognosis. Through this work, we have evaluated the antineoplastic effects of Rhodiola crenulata (R. crenulata) root extracts on the B16-F10 melanoma cell line, both in vitro and in vivo. We observed that R. crenulata treatment resulted in increased cell death as well as a reduction in tumor cell proliferation and migration in vitro. Additionally, we observed that R. crenulata decreased the expression of integrin ß1 and vimentin and increased the expression of E-cadherin. Further, in mice treated with a topical R. crenulata-based cream therapy, tumors were more likely to have a radial growth pattern, a reduction in mitotic activity, and an increase in tumor necrosis. We also observed that mice drinking water supplemented with R. crenulata displayed a reduction of metastatic foci in disseminated models of melanoma. Collectively, these findings suggest that R. crenulata exhibits striking antitumorigenic and antimetastatic properties and that this extract may harbor potential novel adjuvant therapy for the treatment of melanoma.

Rhodiola crenulata inhibits Wnt/ß-catenin signaling in glioblastoma.

BACKGROUND: Rhodiola crenulata is a perennial plant that grows in the high altitudes of Eastern Europe and Asia. R crenulata has been used for many years in Eastern traditional medicine for a variety of medicinal purposes and it has been shown to elicit antineoplastic effects. The purpose of this study is to determine if R crenulata extract exhibits antitumor properties on glioblastoma multiforme (GBM), the most common and aggressive primary brain tumor. MATERIALS AND METHODS: Human U87 GBM cells were treated with 200 µg/mL of R crenulata or vehicle control. Cell proliferation was measured via MTS assay and clonogenic assay. The expressions of glial fibrillary acidic protein, a protein marker of differentiation, E-cadherin, and non-phospho active ß-catenin were measured with immunocytochemistry. Neurosphere assay was performed in low attachment plates. Activity of the Wnt/ß-catenin transcriptional activation was assessed via a dual-luciferase assay. RESULTS: MTS and clonogenicity assays revealed a decrease in proliferation with R crenulata therapy with an increased sensitivity to radiation. Immunocytochemistry revealed that R crenulata induced glial fibrillary acidic protein and E-cadherin expression suggestive of a more differentiated state. In agreement with the change in differentiation neurosphere formation was decreased upon treatment with R crenulata. ß-Catenin dual reporter assay revealed a decrease in Wnt promoter activity after treatment with R crenulata; this was supported by a decrease in nuclear localization of ß-catenin. CONCLUSIONS: Treatment with R crenulata extract effectively suppresses proliferation, stimulates differentiation, and eliminates tumorsphere formation of GBM cells in vitro. The observed effects are associated with inhibition of Wnt/ß-catenin signaling pathway.

Motor practice effects and sensorimotor integration in adults who stutter: Evidence from visuomotor tracking performance.

PURPOSE: The purpose of this study was to utilize a visuomotor tracking task, with both the jaw and hand, to add to the literature regarding non-speech motor practice and sensorimotor integration (outside of auditory-motor integration domain) in adults who do (PWS) and do not (PWNS) stutter. METHOD: Participants were 15 PWS (14 males, mean age = 27.0) and 15 PWNS (14 males, mean age = 27.2). Participants tracked both predictable and unpredictable moving targets separately with their jaw and their dominant hand, and accuracy was assessed by calculating phase and amplitude difference between the participant and the target. Motor practice effect was examined by comparing group performance over consecutive tracking trials of predictable conditions as well as within the first trial of same conditions. RESULTS: Results showed that compared to PWNS, PWS were not significantly different in matching either the phase (timing) or the amplitude of the target in both jaw and hand tracking of predictable and unpredictable targets. Further, there were no significant between-group differences in motor practice effects for either jaw or hand tracking. Both groups showed improved tracking accuracy within and between the trials. CONCLUSION: Our findings revealed no statistically significant differences in non-speech motor practice effects and integration of sensorimotor feedback between PWS and PWNS, at least in the context of the visuomotor tracking tasks employed in the study. In general, both talker groups exhibited practice effects (i.e., increased accuracy over time) within and between tracking trials during both jaw and hand tracking. Implications for these results are discussed. EDUCATIONAL OBJECTIVES: The reader will be able to: (a) describe the importance of motor learning and sensory-motor integration for speech, (b) summarize past research on PWS's performance during speech and nonspeech motor tasks, and (c) describe the relation between different aspects of speech and non-speech motor control and stuttering.

Outcomes of Children with Hearing Loss: Data Collection and Methods.

OBJECTIVES: The primary objective of this article was to describe recruitment, data collection, and methods for a longitudinal, multicenter study involving children with bilateral mild to severe hearing loss. The goals of this research program were to characterize the developmental outcomes of children with mild to severe bilateral hearing loss during infancy and the preschool years. Furthermore, the researchers examined how these outcomes were associated with the child's hearing loss and how home background and clinical interventions mediated and moderated these outcomes. DESIGN: The participants in this study were children who are hard of hearing (CHH) and children with normal hearing (CNH) who provided comparison data. CHH were eligible for participation if (1) their chronological age was between 6 months and 7 years of age at the time of recruitment, (2) they had a better-ear pure-tone average of 25 to 75 dB HL, (3) they had not received a cochlear implant, (4) they were from homes where English was the primary language, and (5) they did not demonstrate significant cognitive or motor delays. Across the time span of recruitment, 430 parents of potential children with hearing loss made contact with the research group. This resulted in 317 CHH who qualified for enrollment. In addition, 117 CNH qualified for enrollment. An accelerated longitudinal design was used, in which multiple age cohorts were followed long enough to provide overlap. Specifically, children were recruited and enrolled continuously across an age span of 6.5 years and were followed for at least 3 years. This design allowed for tests of time (period) versus cohort age effects that could arise by changes in services and technology over time, yet still allowed for examination of important developmental relationships. RESULTS: The distribution of degree of hearing loss for the CHH showed that the majority of CHH had moderate or moderate-to-severe hearing losses, indicating that the sample undersampled children with mild HL. For mothers of both CHH and CNH, the distribution of maternal education level showed that few mothers lacked at least a high school education and a slight majority had completed a bachelor's degree, suggesting that this sample of research volunteers was more advantaged than the United States population. The test battery consisted of a variety of measures concerning participants' hearing and behavioral development. These data were gathered in sessions during which the child was examined by an audiologist and a speech-language examiner. In addition, questionnaires concerning the child's behavior and development were completed by the parents. CONCLUSION: The Outcomes of Children with Hearing Loss study was intended to examine the relationship between variation in hearing ability across children with normal and mild to severe hearing loss and variation in their outcomes across several domains of development. In addition, the research team sought to document important mediators and moderators that act between the hearing loss and the outcomes. Because the study design provided for the examination of outcomes throughout infancy and early childhood, it was necessary to employ a number of different measures of the same construct to accommodate changes in developmental performance across age. This resulted in a large matrix of measures across variable types and developmental levels, as described in this manuscript.

Nonlinear frequency compression in hearing aids: impact on speech and language development.

OBJECTIVES: The research questions of this study were: (1) Are children using nonlinear frequency compression (NLFC) in their hearing aids getting better access to the speech signal than children using conventional processing schemes? The authors hypothesized that children whose hearing aids provided wider input bandwidth would have more access to the speech signal, as measured by an adaptation of the Speech Intelligibility Index, and (2) are speech and language skills different for children who have been fit with the two different technologies; if so, in what areas? The authors hypothesized that if the children were getting increased access to the speech signal as a result of their NLFC hearing aids (question 1), it would be possible to see improved performance in areas of speech production, morphosyntax, and speech perception compared with the group with conventional processing. DESIGN: Participants included 66 children with hearing loss recruited as part of a larger multisite National Institutes of Health-funded study, Outcomes for Children with Hearing Loss, designed to explore the developmental outcomes of children with mild to severe hearing loss. For the larger study, data on communication, academic and psychosocial skills were gathered in an accelerated longitudinal design, with entry into the study between 6 months and 7 years of age. Subjects in this report consisted of 3-, 4-, and 5-year-old children recruited at the North Carolina test site. All had at least at least 6 months of current hearing aid usage with their NLFC or conventional amplification. Demographic characteristics were compared at the three age levels as well as audibility and speech/language outcomes; speech-perception scores were compared for the 5-year-old groups. RESULTS: Results indicate that the audibility provided did not differ between the technology options. As a result, there was no difference between groups on speech or language outcome measures at 4 or 5 years of age, and no impact on speech perception (measured at 5 years of age). The difference in Comprehensive Assessment of Spoken Language and mean length of utterance scores for the 3-year-old group favoring the group with conventional amplification may be a consequence of confounding factors such as increased incidence of prematurity in the group using NLFC. CONCLUSIONS: Children fit with NLFC had similar audibility, as measured by a modified Speech Intelligibility Index, compared with a matched group of children using conventional technology. In turn, there were no differences in their speech and language abilities.

Why words are hard for adults with developmental language impairments.

PURPOSE: To determine whether word learning problems associated with developmental language impairment (LI) reflect deficits in encoding or subsequent remembering of forms and meanings. METHOD: Sixty-nine 18- to 25-year-olds with LI or without (the normal development [ND] group) took tests to measure learning of 16 word forms and meanings immediately after training (encoding) and 12 hr, 24 hr, and 1 week later (remembering). Half of the participants trained in the morning, and half trained in the evening. RESULTS: At immediate posttest, participants with LI performed more poorly on form and meaning than those with ND. Poor performance was more likely among those with more severe LI. The LI-ND gap for word form recall widened over 1 week. In contrast, the LI and ND groups demonstrated no difference in remembering word meanings over the week. In both groups, participants who trained in the evening, and therefore slept shortly after training, demonstrated greater gains in meaning recall than those who trained in the morning. CONCLUSIONS: Some adults with LI have encoding deficits that limit the addition of word forms and meanings to the lexicon. Similarities and differences in patterns of remembering in the LI and ND groups motivate the hypothesis that consolidation of declarative memory is a strength for adults with LI.

Phonetically governed voicing onset and offset in preschool children who stutter.

UNLABELLED: Phonetically governed changes in the fundamental frequency (F0) of vowels that immediately precede and follow voiceless stop plosives have been found to follow consistent patterns in adults and children as young as four years of age. In the present study, F0 onset and offset patterns in 14 children who stutter (CWS) and 14 children who do not stutter (CWNS) were investigated to evaluate differences in speech production. Participants produced utterances containing two VCV sequences. F0 patterns in the last ten vocal cycles in the preceding vowel (voicing offset) and the first ten vocal cycles in the subsequent vowel (voicing onset) were analyzed. A repeated measures ANOVA revealed no group differences between the CWS and CWNS in either voicing onset or offset gestures. Both groups showed patterns of F0 onset and offset that were consistent with the mature patterns seen in children and adults in previous studies. These findings suggest that in both CWS and CWNS, a mature pattern of voicing onset and offset is present by age 3;6. This study suggests that there is no difference between CWS and CWNS in the coordination of respiratory and laryngeal systems during voicing onset or offset. EDUCATIONAL OBJECTIVES: The reader will be able to: (a) discuss the importance of investigating children who stutter close to the onset of stuttering; (b) describe the typical change in F0 during voicing onset; (c) discuss the potential implications of these results with regard to future research.

GATA3 inhibits breast cancer metastasis through the reversal of epithelial-mesenchymal transition.

GATA3, a transcription factor that regulates T lymphocyte differentiation and maturation, is exclusively expressed in early stage well differentiated breast cancers but not in advanced invasive cancers. However, little is understood regarding its activity and the mechanisms underlying this differential expression in cancers. Here, we employed GATA3-positive, non-invasive (MCF-7) and GATA3-negative, invasive (MDA-MB-231) breast cancer cells to define its role in the transformation between these two distinct phenotypes. Ectopic expression of GATA3 in MDA-MB-231 cells led to a cuboidal-like epithelial phenotype and reduced cell invasive activity. These cells also increased E-cadherin expression but decreased levels of vimentin, N-cadherin, and MMP-9. Further, MDA-MB-231 cells expressing GATA3 grew smaller primary tumors without metastasis compared with larger metastatic tumors derived from control MDA-MB-231 cells in xenografted mice. GATA3 was found to induce E-cadherin expression through binding GATA-like motifs located in the E-cadherin promoter. Blockade of GATA3 using small interfering RNA gene knockdown in MCF-7 cells triggered fibroblastic transformation and cell invasion, resulting in distant metastasis. Studies of human breast cancer showed that GATA3 expression correlated with elevated E-cadherin levels, ER expression, and long disease-free survival. These data suggest that GATA3 drives invasive breast cancer cells to undergo the reversal of epithelial-mesenchymal transition, leading to the suppression of cancer metastasis.

Pathways contributing to development of spontaneous mammary tumors in BALB/c-Trp53+/- mice.

Mutation and loss of function in p53 are common features among human breast cancers. Here we use BALB/c-Trp53+/- mice as a model to examine the sequence of events leading to mammary tumors. Mammary gland proliferation rates were similar in both BALB/c-Trp53+/- mice and wild-type controls. In addition, sporadic mammary hyperplasias were rare in BALB/c-Trp53+/- mice and not detectably different from those of wild-type controls. Among the 28 mammary tumors collected from BALB/c-Trp53+/- mice, loss of heterozygosity for Trp53 was detected in more than 90% of invasive mammary tumors. Transplantation of Trp53+/- ductal hyperplasias also indicated an association between loss of the wild-type allele of Trp53 and progression to invasive carcinomas. Therefore, loss of p53 function seems to be a rate-limiting step in progression. Moreover, expression of biomarkers such as estrogen receptor alpha, progesterone receptor, Her2/Neu, and activated Notch1 varied among mammary tumors, suggesting that multiple oncogenic lesions collaborate with loss of p53 function. Expression of biomarkers was retained when tumor fragments were transplanted to syngeneic hosts. Tumors expressing solely luminal or basal keratins were also observed (27 and 11%, respectively), but the largest class of tumors expressed both luminal and basal keratins (62%). Overall, this panel of transplantable tumors provides a resource for detailed evaluation of the cell lineages undergoing transformation and preclinical testing of therapeutic agents targeting a variety of oncogenic pathways including cancer stem cells.