Purpose. This study reports the development and clinical trial of a new treatment program for persistent developmental stuttering in adolescents and adults. The treatment is based on the operant ...procedure of self-imposed time-out. This involves the person stopping speaking for a short period after each stutter.
Method. Twenty-two participants completed Stage 1 (Instatement and Generalisation) of the program and 18 completed Stage 2 (Maintenance) of the program. Stuttering outcome was measured from independent audio and video recordings made outside and inside the clinic, before and after treatment. Speech naturalness was measured at the end of Stage 1. Secondary analyses were conducted to investigate whether responsiveness to the program was related to stuttering severity or age. Participants completed an extensive self-report inventory at the end of treatment.
Results. There was a range of responsiveness to the treatment, with more than half the participants reducing their stuttering by more than 50%. Participants with more severe types of stuttering appeared to respond better but no other predictors of responsiveness were identified. Speech sounded reasonably natural after treatment. Participants' perceptions of the treatment were for the most part positive with the majority reporting that the treatment was easier to use and more effective than treatment based on prolonged-speech.
Conclusions. The self-imposed time-out treatment program reported here is clearly effective for a significant number of adolescents and adults who stutter. Given that it does not require speech restructuring and the constant attention to speech that this involves, this could be a treatment of choice for those who are likely to respond. Consequently, further research is needed to determine which clients seeking behavioural treatment for their stuttering will benefit most from this program. Further research is also needed to determine the extent to which the effectiveness of time-out is increased when combined with other behavioural treatments.
This study explored an alternative methodology for analyzing communication interactions, to determine whether it could be applied to interventions designed to improve the communication competence of ...university graduates who are non-native speakers of English (NNSE). Qualitative research methods examined the communication of both interlocutors in job interviews to determine if there was a relationship between performance and perceptual judgements of accent, intelligibility, comprehensibility and employability. Detailed conversational analysis allowed for in-depth consideration of typical conversation breakdown and repair strategies used by native speakers of English (NSE) and NNSE. The results indicated that the majority of participant errors were accent differences and minor grammatical errors. The type and quantity of repair strategies utilized in response to the errors varied depending on communication and interactional competence. We predicted that there would be a relationship between participant's performance and interlocutor's perceptions. This proved to be the case in the NSE-NNSE interactions, but not in the NSE-NSE interview. This methodology offers a promising framework which could be utilized in future investigations into communication skills of NNSE and their interlocutors. Analyzing data from a job interview provided preliminary information about the context contingent aspects of communication that are problematic for graduates who are NNSE.
Living in the transformative age is one of disruption, change, and infinite opportunity. However, living in a cloud-based world with self-driving cars, advanced robotics, artificial intelligence, ...e-health, 3-D printing, and COVID-19 can also be somewhat daunting, challenging, and even confronting. As speech-language pathologists, researchers, educators, and advocates, we need to be agile, more creative and connected to data, experiences, and people. Now more than ever, these connections will enable transformation and ensure the future of our profession.
speech-language pathologists are now practising on a global scale, in multiple languages and unique contexts, and the education of our future workforce is critical. Over the past 10 years, there has been rapid growth in the number of speech-language pathology training programs delivered by universities in Australia, as well as a significant shift in the demand for services and changing employment opportunities. In Australia, the profession has been planning for the future; Making Futures Happen, Building a Future workforce, and re-developing our Professional Standards. But, are we really cognisant of the global challenges and opportunities for our profession? Do we really value global connectivity?
In this discussion paper, authentic examples and plausible scenarios are being used to explore the global transformation of the speech-language pathology profession. Each will highlight some of the political, economic, societal, cultural, and technological influences on speech-language pathology research, teaching, and practices that are driving development, change, and innovation. Readers will be challenged to consider how thinking globally, with a focus on context, translation, and connection will enable them to rise to the challenges we face today and forge new paths for the future.
Abstract
Context
Congenital hyperinsulinism (HI) is characterized by inappropriate insulin secretion despite low blood glucose. Persistent HI is often monogenic, with the majority of cases diagnosed ...in infancy. Less is known about the contribution of monogenic forms of disease in those presenting in childhood.
Objective
We investigated the likelihood of finding a genetic cause in childhood-onset HI and explored potential factors leading to later age at presentation of disease.
Methods
We screened known disease-causing genes in 1848 individuals with HI, referred for genetic testing as part of routine clinical care. Individuals were classified as infancy-onset (diagnosed with HI < 12 months of age) or childhood-onset (diagnosed at age 1-16 years). We assessed clinical characteristics and the genotypes of individuals with monogenic HI diagnosed in childhood to gain insights into the later age at diagnosis of HI in these children.
Results
We identified the monogenic cause in 24% (n = 42/173) of the childhood-onset HI cohort; this was significantly lower than the proportion of genetic diagnoses in infancy-onset cases (74.5% n = 1248/1675, P < 0.00001). Most (75%) individuals with genetically confirmed childhood-onset HI were diagnosed before 2.7 years, suggesting these cases represent the tail end of the normal distribution in age at diagnosis. This is supported by the finding that 81% of the variants identified in the childhood-onset cohort were detected in those diagnosed in infancy.
Conclusion
We have shown that monogenic HI is an important cause of hyperinsulinism presenting outside of infancy. Genetic testing should be considered in children with persistent hyperinsulinism, regardless of age at diagnosis.
Congenital hyperinsulinism is characterised by the inappropriate release of insulin during hypoglycaemia. This potentially life-threatening disorder can occur in isolation, or present as a feature of ...syndromic disease. Establishing the underlying aetiology of the hyperinsulinism is critical for guiding medical management of this condition especially in children with diazoxide-unresponsive hyperinsulinism where the underlying genetics determines whether focal or diffuse pancreatic disease is present. Disease-causing single nucleotide variants affecting over 30 genes are known to cause persistent hyperinsulinism with mutations in the KATP channel genes (
ABCC8
and
KCNJ11
) most commonly identified in children with severe persistent disease. Defects in methylation, changes in chromosome number, and large deletions and duplications disrupting multiple genes are also well described in congenital hyperinsulinism, further highlighting the genetic heterogeneity of this condition. Next-generation sequencing has revolutionised the approach to genetic testing for congenital hyperinsulinism with targeted gene panels, exome, and genome sequencing being highly sensitive methods for the analysis of multiple disease genes in a single reaction. It should though be recognised that limitations remain with next-generation sequencing with no single application able to detect all reported forms of genetic variation. This is an important consideration for hyperinsulinism genetic testing as comprehensive screening may require multiple investigations.
Gene expression is tightly regulated, with many genes exhibiting cell-specific silencing when their protein product would disrupt normal cellular function
. This silencing is largely controlled by ...non-coding elements, and their disruption might cause human disease
. We performed gene-agnostic screening of the non-coding regions to discover new molecular causes of congenital hyperinsulinism. This identified 14 non-coding de novo variants affecting a 42-bp conserved region encompassed by a regulatory element in intron 2 of the hexokinase 1 gene (HK1). HK1 is widely expressed across all tissues except in the liver and pancreatic beta cells and is thus termed a 'disallowed gene' in these specific tissues. We demonstrated that the variants result in a loss of repression of HK1 in pancreatic beta cells, thereby causing insulin secretion and congenital hyperinsulinism. Using epigenomic data accessed from public repositories, we demonstrated that these variants reside within a regulatory region that we determine to be critical for cell-specific silencing. Importantly, this has revealed a disease mechanism for non-coding variants that cause inappropriate expression of a disallowed gene.
Heteroleptic neutral copper(I) dipyrrin complexes have been synthesised with the general formula Cu(4,4'-(R)-6,6'-(CH3)-bipyridine)(dipyrrin), R = CH3 or CO2Et, and H-dipyrrin is either ...1,3,7,9-tetramethyldipyrromethene (HL1), 1,13-diphenyl-6,8-diisoindolemethene (HL2), or 1,13-diphenyl-3,11-di(trifluoromethyl)-6,8-diisoindolemethene (HL3). Improved stability was observed across the series , likely due to better steric constraints between the ligands. Visible light absorption has also been enhanced with a red-shift in absorption from 450 nm to 600 nm. Complex 3 shows photoluminescence lifetime in the order of nanoseconds suggesting singlet fluorescence which is supported by theoretical calculations. Study of the complexes as sensitisers in dye-sensitised solar cells was achieved by assembling the dye in situ on the surface of TiO2 in a series of steps (anchoring ligand followed by ancillary ligand and Cu(CH3CN)4BF4. The highest efficiency achieved was 0.41% for the dye with HL3, attributed to better dye regeneration due to a more favourable oxidation potential.
Objective Mutations in the KATP channel genes, ABCC8 and KCNJ11, are the most common cause of congenital hyperinsulinism. The diagnosis of KATP-hyperinsulinism is important for the clinical ...management of the condition. We aimed to determine the clinical features that help to identify KATP-hyperinsulinism at diagnosis. Design We studied 761 individuals with KATP-hyperinsulinism and 862 probands with hyperinsulinism of unknown aetiology diagnosed before 6 months of age. All were referred as part of routine clinical care. Methods We compared the clinical features of KATP-hyperinsulinism and unknown hyperinsulinism cases. We performed logistic regression and receiver operator characteristic (ROC) analysis to identify the features that predict KATP-hyperinsulinism. Results Higher birth weight, diazoxide unresponsiveness and diagnosis in the first week of life were independently associated with KATP-hyperinsulinism (adjusted odds ratio: 4.5 (95% CI: 3.4–5.9), 0.09 (0.06–0.13) and 3.3 (2.0–5.0) respectively). Birth weight and diazoxide unresponsiveness were additive and highly discriminatory for identifying KATP-hyperinsulinism (ROC area under the curve for birth weight 0.80, diazoxide responsiveness 0.77, and together 0.88, 95% CI: 0.85–0.90). In this study, 86% born large for gestation and 78% born appropriate for gestation and who did not respond to diazoxide treatment had KATP-hyperinsulinism. In contrast, of those individuals born small for gestation, none who were diazoxide responsive and only 4% of those who were diazoxide unresponsive had KATP-hyperinsulinism. Conclusions Individuals with hyperinsulinism born appropriate or large for gestation and unresponsive to diazoxide treatment are most likely to have an ABCC8 or KCNJ11 mutation. These patients should be prioritised for genetic testing of KATP channel genes.
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