The Communication Benefits of Participation in Camp Dream. Speak. Live.: An Extension and Replication.

School-based guidelines often require that treatment focuses on minimizing or eliminating stuttered speech. The purpose of this study was to examine the benefits of explicit training in communication competencies to children who stutter without targeting stuttered speech. Thirty-seven children (ages 4-16) completed Camp Dream. Speak. Live., an intensive group treatment program which targets the psychosocial needs and communication of children who stutter. Outcome measures included the Overall Assessment of the Speaker's Experience of Stuttering (OASES), the Communication Attitude Test for Preschool and Kindergarten Children Who Stutter (KiddyCAT), and the Patient Reported Measurement Information System (PROMIS) Pediatric Peer Relationships Short Form (PROMIS Peer Relationships) and Parent Proxy Peer Relationships Short Form (PROMIS Parent Proxy). Pre- and posttreatment public presentations were rated on nine core verbal and nonverbal communication competencies by a neutral observer. Similar to previous studies, participants demonstrated significant improvements in communication attitudes (OASES) and perceived ability to establish peer relationships (PROMIS Peer Relationships), particularly school-aged participants (ages 7-16). Participants also demonstrated significant improvement in eight of the nine communication competencies. Findings suggest that, in addition to the psychosocial gains of programs such as Camp Dream. Speak. Live., children who stutter benefit from explicit training in communication skills, and these gains are not dependent on the presence of stuttered speech.

Vocal overimitation in preschool-age children.

Overimitation--copying incorrect, idiosyncratic, or causally irrelevant actions--has been linked to our species' long history with artifacts whose functions are often opaque. It is an open question, however, whether children overimitate outside the artifact domain. We explored this question by presenting preschool-age children (3- to 5-year-olds, N=120) with an elicited imitation task that included high- and low-frequency disyllabic nouns (e.g., 'pizza) and nonwords (e.g., 'chizza), all of which had a stressed first syllable. However, during testing, half of the stimuli were incorrectly pronounced by stressing the second syllable (e.g., pi'zza). More than half of the children copied the model's incorrect pronunciation of high-frequency familiar words, consistent with overimitation. This pattern of response persisted even after children had themselves correctly named the familiar words prior to the start of testing, confirming that children purposefully altered the pronunciation of known words to match the incorrect pronunciations used by a model. These results demonstrate that overimitation is not restricted to the artifact domain and might extend to many different tasks and domains.

Investigating Narrative Performance in Children With Developmental Language Disorder: A Systematic Review and Meta-Analysis.

PURPOSE: Narrative assessment is one potentially underutilized and inconsistent method speech-language pathologists may use when considering a diagnosis of developmental language disorder (DLD). However, narration research encompasses many varied methodologies. This systematic review and meta-analysis aimed to (a) investigate how various narrative assessment types (e.g., macrostructure, microstructure, and internal state language) differentiate children with typical development (TD) from children with DLD, (b) identify specific narrative assessment measures that result in greater group differences, and (c) evaluate participant and sample characteristics that may influence performance differences. METHOD: Electronic databases (PsycINFO, ERIC, and PubMed) and ASHAWire were searched on July 30, 2019, to locate studies that reported oral narrative language measures for both DLD and TD groups between ages 4 and 12 years; studies focusing on written narration or other developmental disorders only were excluded. We extracted data related to sample participants, narrative task(s) and assessment measures, and research design. Group differences were quantified using standardized mean differences. Analyses used mixed-effects meta-regression with robust variance estimation to account for effect size dependencies. RESULTS: Searches identified 37 eligible studies published between 1987 and 2019, including 382 effect sizes. Overall meta-analysis showed that children with DLD had decreased narrative performance relative to TD peers, with an overall average effect of -0.82 SD, 95% confidence interval [-0.99, -0.66]. Effect sizes showed significant heterogeneity both between and within studies, even after accounting for effect size-, sample-, and study-level predictors. Across model specifications, grammatical accuracy (microstructure) and story grammar (macrostructure) yielded the most consistent evidence of TD-DLD group differences. CONCLUSIONS: Present findings suggest some narrative assessment measures yield significantly different performance between children with and without DLD. However, researchers need to improve consistency of inclusionary criteria, descriptions of sample characteristics, and reporting of correlations between measures to determine which assessment measures reliably distinguish between groups. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.21200380.

Comparing evaluations of social situations for adults who do and do not stutter.

PURPOSE: Numerous research studies indicate that stuttering is associated with increased risk for social anxiety disorder (SAD). Interpretation bias is one of four cognitive biases thought to maintain symptoms associated with SAD. Interpretation bias occurs when one evaluates social situations as more negative than they actually are. The purpose of this study was to investigate if adults who do and do not stutter interpret positive, ambiguous, mildly negative, and profoundly negative social situations similarly, or-if like individuals with SAD-adults who stutter exhibit negative interpretation biases. METHOD: Forty-eight adults who stutter and 42 age-and gender-matched adults who do not stutter participated. Participants completed the Fear of Negative Evaluation (FNE) and were assigned to one of four groups: adults who stutter with high FNE (AWS-High), adults who stutter with low FNE (AWS-Low), adults who do not stutter with high FNE (AWNS-High), and adults who do not stutter with low FNE (AWNS-Low). All participants completed the trait scale of the State Trait Anxiety Inventory (STAI) and the Interpretation and Judgmental Questionnaire (IJQ). The IJQ contains descriptions of four types of social situations: positive, mildly negative, profoundly negative, and ambiguous. Within each situation type there are five different scenarios, for a total of 20 scenarios across the four situation types. Participants provided written responses to these 20 social scenarios. Qualitative analyses were used to understand how members of each group interpreted the different social scenarios. RESULTS: Thematic analysis revealed that each group responded in similar ways to each of the social scenarios, regardless of the type of situation. Adults who do and do not stutter with low and high FNE agreed on many themes related to the 20 social scenarios, and they agreed across all four types of social situations. Somewhat surprisingly, the theme "stuttering" was mentioned infrequently by the adults who stutter. CONCLUSIONS: Results suggested that adults who do and do not stutter with low and high FNE interpret social situations similarly, and that no group demonstrated a negative interpretation bias consistent with what is observed in adults with SAD. The interpretations provided by each group were appropriate to the specific scenarios being evaluated.

Pharmacological targeting of glucagon and glucagon-like peptide 1 receptors has different effects on energy state and glucose homeostasis in diet-induced obese mice.

Pharmacologic contributions of directly agonizing glucagon-like peptide 1 (GLP-1) receptor or antagonizing glucagon receptor (GCGR) on energy state and glucose homeostasis were assessed in diet-induced obese (DIO) mice. Metabolic rate and respiratory quotient (RQ), hyperglycemic clamp, stable isotope-based dynamic metabolic profiling (SiDMAP) studies of (13)C-labeled glucose during glucose tolerance test (GTT) and gene expression were assessed in cohorts of DIO mice after a single administration of GLP-1 analog [GLP-1-(23)] or anti-GCGR antibody (Ab). GLP-1-(23) and GCGR Ab similarly improved GTT. GLP-1-(23) decreased food intake and body weight trended lower. GCGR Ab modestly decreased food intake without significant effect on body weight. GLP-1-(23) and GCGR Ab decreased RQ with GLP-1, causing a greater effect. In a hyperglycemic clamp, GLP-1-(23) reduced hepatic glucose production (HGP), increased glucose infusion rate (GIR), increased glucose uptake in brown adipose tissue, and increased whole-body glucose turnover, glycolysis, and rate of glycogen synthesis. GCGR Ab slightly decreased HGP, increased GIR, and increased glucose uptake in the heart. SiDMAP showed that GLP-1-(23) and GCGR Ab increased (13)C lactate labeling from glucose, indicating that liver, muscle, and other organs were involved in the rapid disposal of glucose from plasma. GCGR Ab and GLP-1-(23) caused different changes in mRNA expression levels of glucose- and lipid metabolism-associated genes. The effect of GLP-1-(23) on energy state and glucose homeostasis was greater than GCGR Ab. Although GCGR antagonism is associated with increased circulating levels of GLP-1, most GLP-1-(23)-associated pharmacologic effects are more pronounced than GCGR Ab.

Predictors of communication attitude in preschool-age children who stutter.

PURPOSE: Although preschool-age children who stutter report more negative attitudes toward communication than their typically fluent peers, few investigations have explored factors that may contribute to the differences observed in communication attitude. The purpose of the present study was to explore whether behavioral characteristics of stuttering severity (frequency, duration, physical concomitants) and time since onset of stuttering predict communication attitude in preschool-age children. METHOD: Fifty-nine preschool-aged children who stutter completed two speaking samples and the KiddyCAT, a self-report assessment of communication attitude. Speech samples were analyzed for stuttering frequency (measured by percentage of stuttered syllables), duration, and presence of physical concomitants. Linear regression models were used to assess if these behavioral measures of stuttering and time since onset of stuttering predicted self-reported communication attitude. RESULTS: Results indicate stuttering behavioral measures and time since onset do not predict KiddyCAT scores of preschool-age children who stutter. CONCLUSIONS: Preliminary data suggest children who have presented with stuttering for a longer period of time are no more likely to report a negative communication attitude than children who have a shorter time since onset. Additionally, in contrast to school-age children who stutter, but similar to adults and adolescents who stutter, communication attitude is not linearly related to stuttering severity in preschool-age children.

Preliminary study of self-perceived communication competence amongst adults who do and do not stutter.

PURPOSE: Adults who stutter report a significant impact of stuttering on their quality of life, including negative thoughts and attitudes toward communication. In addition to this impact, adolescents who stutter also report lower levels of self-perceived communication competence (SPCC) compared to fluent peers. The purpose of this study was to extend the investigation of SPCC to adults who do and do not stutter. Additional aims investigated included if 1) SPCC predicted overall impact of stuttering, and, 2) stuttering frequency predicted SPCC among adults who stutter. METHODS: Twenty-four adults who stutter and twenty-seven adults who do not stutter matched for age, gender, and education completed the Self-Perceived Communication Competence Scale (Richmond & McCroskey, 1997). All participants who stutter completed the Overall Assessment of the Speaker's Experience of Stuttering (OASES [ages 18+]; Yaruss & Quesal, 2006) and speaking samples to measure stuttering frequency. RESULTS: Adults who stutter reported significantly lower SPCC scale total scores than adults who do not stutter. For adults who stutter, lower SPCC scale scores significantly predicted more severe overall impact of stuttering as measured by the OASES. Stuttering frequency did not predict SPCC scale scores. DISCUSSION: This is the first study to report differences in self-perceived communication competence between adults who do and do not stutter. Results suggest adults who stutter report lower self-perceived communication competence compared to adults who do not stutter. Adults who perceive themselves to have greater communication competence reported less severe overall impact of stuttering, and stuttering frequency did not influence SPCC. Clinical implications for intervention are discussed.

Glucagon receptor antagonist-mediated improvements in glycemic control are dependent on functional pancreatic GLP-1 receptor.

Antagonism of the glucagon receptor (GCGR) is associated with increased circulating levels of glucagon-like peptide-1 (GLP-1). To investigate the contribution of GLP-1 to the antidiabetic actions of GCGR antagonism, we administered an anti-GCGR monoclonal antibody (mAb B) to wild-type mice and GLP-1 receptor knockout (GLP-1R KO) mice. Treatment of wild-type mice with mAb B lowered fasting blood glucose, improved glucose tolerance, and enhanced glucose-stimulated insulin secretion during an intraperitoneal glucose tolerance test (ipGTT). In contrast, treatment of GLP-1R KO mice with mAb B had little efficacy during an ipGTT. Furthermore, pretreatment with the GLP-1R antagonist exendin-(9-39) diminished the antihyperglycemic effects of mAb B in wild-type mice. To determine the mechanism whereby mAb B improves glucose tolerance, we generated a monoclonal antibody that specifically antagonizes the human GLP-1R. Using a human islet transplanted mouse model, we demonstrated that pancreatic islet GLP-1R signaling is required for the full efficacy of the GCGR antagonist. To identify the source of the elevated GLP-1 observed in GCGR mAb-treated mice, we measured active GLP-1 content in pancreas and intestine from db/db mice treated with anti-GCGR mAb for 8 wk. Elevated GLP-1 in GCGR mAb-treated mice was predominantly derived from increased pancreatic GLP-1 synthesis and processing. All together, these data show that pancreatic GLP-1 is a significant contributor to the glucose-lowering effects observed in response to GCGR antagonist treatment.

Pediatrician Referral Practices for Children Who Stutter.

Purpose Given the marked increase in evidence-based information regarding the nature/treatment of stuttering, coupled with the fact that pediatricians tend to be one of the initial points of contact for parents who suspect their preschool-age child may stutter, this study explored pediatricians' (a) accuracy in identifying children who may stutter and (b) likelihood of referring children who present with a profile indicative of stuttering to speech-language pathologists. Method Pediatricians recruited nationally through professional organizations completed a 5- to 7-min online survey that probed stuttering identification and referral practices via responses to experimental case vignettes. Each vignette featured a 4-year-old boy with a family history of stuttering whose mother reported signs of stuttering and manipulation of two factors: stuttering during the pediatrician visit (or not) and negative communication attitude (or not). Results Our findings suggest pediatricians' identification and referral of children who may stutter is largely prompted by observation of overt speech behaviors and/or negative communication attitude. Participants' gender, years in practice, and experience working with children who stutter did not influence likelihood of referral. Conclusions Results indicate pediatricians are less likely to implement a "wait and see" approach with young children who stutter today than in the past. Unlike other common child onset diagnoses, however, parent report of atypical behavior does not yield pediatrician referral to a specialist. Future education and advocacy efforts directed toward pediatricians should emphasize inclusion of factors other than direct observation of stuttering behavior that may warrant referral (e.g., parent report).

Long-term inhibition of the glucagon receptor with a monoclonal antibody in mice causes sustained improvement in glycemic control, with reversible alpha-cell hyperplasia and hyperglucagonemia.

Uncontrolled hepatic glucose output (HGO) contributes significantly to the pathological hyperglycemic state of patients with type 2 diabetes. Glucagon, through action on its receptor, stimulates HGO, thereby leading to increased glycemia. Antagonizing the glucagon signaling pathway represents an attractive therapeutic approach for the treatment of type 2 diabetes. We previously reported the generation and characterization of several high-affinity monoclonal antibodies (mAbs) targeting the glucagon receptor (GCGR). In the present study, we demonstrate that a 5-week treatment of diet-induced obese mice with mAb effectively normalized nonfasting blood glucose. Similar treatment also reduced fasting blood glucose without inducing hypoglycemia or other undesirable metabolic perturbations. In addition, no hypoglycemia was found in db/db mice that were treated with a combination of insulin and mAb. Long-term treatment with the mAb caused dose-dependent hyperglucagonemia and minimal to mild alpha-cell hyperplasia in lean mice. There was no evidence of pancreatic alpha-cell neoplastic transformation in mice treated with mAb for as long as 18 weeks. Treatment-induced hyperglucagonemia and alpha-cell hyperplasia were reversible after treatment withdrawal for periods of 4 and 10 weeks, respectively. It is noteworthy that pancreatic beta-cell function was preserved, as demonstrated by improved glucose tolerance throughout the 18-week treatment period. Our studies further support the concept that long-term inhibition of GCGR signaling by a mAb could be an effective approach for controlling diabetic hyperglycemia.

Fully human monoclonal antibodies antagonizing the glucagon receptor improve glucose homeostasis in mice and monkeys.

Antagonizing the glucagon signaling pathway represents an attractive therapeutic approach for reducing excess hepatic glucose production in patients with type 2 diabetes. Despite extensive efforts, there is currently no human therapeutic that directly inhibits the glucagon/glucagon receptor pathway. We undertook a novel approach by generating high-affinity human monoclonal antibodies (mAbs) to the human glucagon receptor (GCGR) that display potent antagonistic activity in vitro and in vivo. A single injection of a lead antibody, mAb B, at 3 mg/kg, normalized blood glucose levels in ob/ob mice for 8 days. In addition, a single injection of mAb B dose-dependently lowered fasting blood glucose levels without inducing hypoglycemia and improved glucose tolerance in normal C57BL/6 mice. In normal cynomolgus monkeys, a single injection improved glucose tolerance while increasing glucagon and active glucagon-like peptide-1 levels. Thus, the anti-GCGR mAb could represent an effective new therapeutic for the treatment of type 2 diabetes.

Design and synthesis of conformationally constrained glucagon-like peptide-1 derivatives with increased plasma stability and prolonged in vivo activity.

A series of conformationally constrained derivatives of glucagon-like peptide-1 (GLP-1) were designed and evaluated. By use of [Gly (8)]GLP-1(7-37)-NH2 (2) peptide as a starting point, 17 cyclic derivatives possessing i to i + 4, i to i + 5, or i to i + 7 side chain to side chain lactam bridges from positions 18 to 30 were prepared. The effect of a helix-promoting alpha-amino-isobutyric acid (Aib) substitution at position 22 was also evaluated. The introduction of i to i + 4 glutamic acid-lysine lactam constraints in c[Glu (18)-Lys (22)][Gly (8)]GLP-1(7-37)-NH2 (6), c[Glu (22)-Lys (26)][Gly (8)]GLP-1(7-37)-NH2 (10), and c[Glu (23)-Lys (27)][Gly (8)]GLP-1(7-37)-NH2 (11) resulted in potent functional activity and receptor affinities comparable to native GLP-1. Selected GLP-1 peptides were chemoselectively PEGylated in order to prolong their in vivo activity. PEGylated peptides [Gly (8),Aib (22)]GLP-1(7-37)-Cys ((PEG))-Ala-NH2 (23) and c[Glu (22)-Lys (26)][Gly (8)]GLP-1(7-37)-Cys ((PEG))-Ser-Gly-NH2 (24) retained picomolar functional potency and avid receptor binding properties. Importantly, PEGylated GLP-1 peptide 23 exhibited sustained in vivo efficacy with respect to blood glucose reduction and decreased body weight for several days in nonhuman primates.

Fear of Negative Evaluation, Trait Anxiety, and Judgment Bias in Adults who Stutter.

PURPOSE: Persons who stutter (PWS) and those with social anxiety disorder may exhibit fear of negative evaluation (FNE) and anxiety in social situations. However, the information processing biases that perpetuate these characteristics have had limited investigation. This study investigated judgment bias in social situations. METHOD: Participants included 50 adults who stutter and 45 age- and gender-matched fluent persons who do not stutter (PWNS), who made up the control group. Participants completed the Interpretation and Judgmental Questionnaire (Voncken, Bögels, & deVries, 2003), and threat scores were calculated. RESULTS: There were no significant differences between PWS and PWNS in social threat or nonsocial threat scores. When the PWS group was divided on the basis of FNE and compared with PWNS participants without heightened anxiety (n = 35), the PWS with high FNE had significantly higher total social threat scores than the PWS with low FNE. The three groups did not differ in threat ratings for ambiguous or profoundly negative social situations. CONCLUSIONS: Judgment bias in PWS is mediated by the magnitude of FNE present; not all PWS exhibit judgment bias for social situations. Treatment implications include the need for psychosocial support addressing the negative impacts on quality of life and restrictions on social engagement that stuttering may cause in some individuals.

The effect of lectins on Cryptosporidium parvum oocyst in vitro attachment to host cells.

The influence of lectins on Cryptosporidium parvum oocyst agglutination and on attachment to both fixed Madin Darby Canine Kidney (MDCK) cells and fixed HCT-8 (human colorectal epithelial) cells was examined. Oocyst cell wall characteristics were examined by transmission electron microscopy. Lectin-free oocysts were shown to adhere equally to both MDCK cells and HCT-8 cells. In MDCK cells, the addition of 1-25 microg/ml Codium fragile lectin, 10 microg/ml Maclura pomifera lectin, 10 microg/ml Helix pomatia lectin, and 10-200 microg/ml Artocarpus integrifolia lectin significantly increased attachment to at least 1 of the cell cultures as compared to oocysts incubated without any lectin. The lectin-enhanced attachment was reversed by co-incubation of lectin treated-oocysts with 250 mM of each specific sugar (for a given lectin). In agglutination assays, concentrations as low as 0.5 microg/ml of C. fragile, M. pomifera, and A. integrifolia lectin agglutinated oocysts within 60 min. Finally, in TEM samples, colloidal gold conjugated-lectins from A. integrifolia, C. fragile, H. pomatia, and M. pomifera attached to oocysts, and this could be competitively inhibited by a lectin-specific sugar. This suggests that C. parvum oocysts are highly reactive to N-acetyl galactosamine-binding lectins and that the presence of N-acetyl-galactosamine containing molecules on oocysts can potentially help in oocyst attachment to host cells.

Long-acting FGF21 has enhanced efficacy in diet-induced obese mice and in obese rhesus monkeys.

Fibroblast growth factor 21 (FGF21), a hormone with short half-life, has consistently shown strong pharmacological efficacy. We first assessed the efficacy of murine recombinant FGF21 in C57BL6 lean mice for 5 wk. We then generated a long-acting FGF21 molecule by fusing a Fc to a variant of human recombinant FGF21 (hrFGF21) that contained two engineered mutations [L98R, P171G; Fc-FGF21(RG)] and tested it in C57BL6 diet-induced obese mice and obese rhesus monkeys. We compared its metabolic properties with those of the hrFGF21. Groups of diet-induced obese mice were treated for 36 d with different doses of hrFGF21 (01, 0.3, and 1 mg/kg twice daily) and with Fc-FGF21(RG) (2.3 mg/kg, every 5 d). Body weight, glucose, insulin, cholesterol, and triglyceride levels were decreased after treatment with either compound. A glucose tolerance test (GTT) was also improved. Obese rhesus monkeys were treated with hrFGF21 (once a day) and Fc-FGF21(RG) (once a week) in a dose-escalation fashion. Doses started at 0.1 and 0.3 mg/kg and ended at 3 and 5 mg/kg for hrFGF21 and Fc-FGF21(RG), respectively. Doses were escalated every 2 wk, and animals were followed up for a washout period of 3 wk. Body weight, glucose, insulin, cholesterol, and triglyceride levels and the GTT profile were decreased to a greater extent with Fc-FGF21(RG) than with hrFGF21. The PK-PD relationship of Fc-FGF21(RG) exposure and triglyceride reduction was also conducted with a maximum response model. In conclusion, in more than one species, Fc-FGF21(RG) chronically administered once a week showed similar or greater efficacy than hrFGF21 administered daily.