50 research outputs found
Variability in fricative production of young people with Down's syndrome : an EPG analysis
Speech production in Down's syndrome is highly variable, with particular problems arising from complex articulations such as fricatives. In this paper, EPG analysis is used to study the variation in the production of the fricatives /s/ and /sh/ in 6 young people with Down's syndrome. The variability of these productions is compared with information from the Robbins and Klee Oral/Speech Motor Control Protocol.casl[1] Bleile, K., Schwartz, I. 1984. Three perspectives on the
speech of children with Down's syndrome. Journal of
Communication Disorders 17, 2, 87-94.
[2] Dodd, B., Thompson, L. 2001. Speech Disorder in
children with Down's syndrome. Journal of Intellectual
Disability Research 45, 4, 308-316.
[3] Gibbon, F. 2004. Abnormal patterns of tongue-palate
contact in the speech of individuals with cleft palate.
Clinical Linguistics and Phonetics 18, 4-5, 285-311.
[4] Gibbon, F., Hardcastle, W. 1987. Articulatory description
and treatment of lateral /s/- using Electropalatography: a
case study. British Journal of Disorders of
Communication 22, 203-217.
[5] Gibbon, F. E., McNeill, A. M., Wood, S. E., Watson, J.
M. M. 2003. Changes in linguapalatal contact patterns
during therapy for velar fronting in a 10-year-old with
Down's syndrome. International Journal of
Communication Disorder. 38, 47-64.
[6] Hamilton, C. 1993. Investigation of the articulatory
patterns of young adults with Down's syndrome using
electropalatography. Down's Syndrome: Research and
Practice, 1 (1), 15-28.
[7] Hardcastle, W.J., Gibbon, F. 1997. Electropalatography
and its clinical applications. In: Ball, M. J., Code, C.
(eds), Instrumental Clinical Phonetics. London: Whurr
publishers, 149-193.
[8] Hoole, P., Zeigler, W., Hartmann, E., Hardcastle, W.
1989. Parallel electropalatographic and acoustic measures
of fricatives. Clinical Linguistics and Phonetics 3, 59-69.
[9] Kumin, L. 1996. Speech and Language Skills in Children
with Down Syndrome. Mental Retardation and
Developmental Disabilities 2, 109-115.
[10] McLeod, S., Roberts, A. 2005. Templates of
tongue/palate contact for speech sound intervention. In C.
Heine & L. Brown (Eds). Proceed. Of Speech Pathology
Australia National Conference Melbourne:Speech
Pathology Australia, 104-112.
[11] Mcleod, S., Roberts, A., Sita, J. 2006. Tongue/palate
contact for the production of /s/ and /z/. Clinical
Linguistics and Phonetics, 20, 1, 51-66.
[12] Robbins, J., Klee, T. 1987. Clinical Assessment of
Oropharyngeal Motor Development in Young Children.
Journal of Speech and Hearing Disorders. 52, 271-277
[13] Spender, Q., 1995. Impaired oral-motor function in
children with Down's syndrome: a study of three twin
pairs. European Journal of Disorders of Communication.
30, 77-87.
[14] Tabain, M. 2001. Variability in Fricative Production and
Spectra: Implications for the Hyper- and Hypo- and
Quantal Theories of Speech Production. Language and
Speech 44, 1, 57-94.
[15] Weismer, G. 1997. Motor Speech Disorders. In W. J.
Hardcastle & J. Laver (Eds) The Handbook of Phonetic
Sciences. Oxford: Blackwell, 191-220.pub41pu
Using Electropalatography (EPG) in the assessment and treatment of developmental motor speech disorders: Linking basic and applied research
This series consists of unpublished working-
papers. They are not final versions and may be
superseded by publication in journal or book form,
which should be cited in preference.
All rights remain with the author(s) at this stage,
and circulation of a work in progress in this series
does not prejudice its later publication.
Comments to authors are welcome.Many children experience significant difficulties in developing key aspects of speech. For some, these communication difficulties are compounded by co-occurring intellectual disabilities. This paper presents two case studies from a larger on-going longitudinal study of the
effectiveness of using electropalatography (EPG) to address the intelligibility problems experienced by many children and young people with Down's syndrome (DS). EPG, an innovative computer-based tool for assessing and treating speech motor difficulties, enables the speaker to see- the placement of his or her tongue during speech and to attempt to correct any lingual palatal errors. This visual supplementation of auditory feedback offers potential therapeutic benefits for children with intellectual
disabilities, many of whom show relative strengths in visual versus auditory and simultaneous versus sequential processing (e.g. [1]). EPG also provides therapists with an objective measure of articulatory ability. Findings from these two case studies demonstrate the potential utility of
EPG in both the assessment and treatment of speech motor disorders in DS.caslpub156pubWP-1
The relationship between speech, oromotor, language and cognitive abilities in children with Down's syndrome.
This series consists of unpublished working-
papers. They are not final versions and may be
superseded by publication in journal or book
form, which should be cited in preference.
All rights remain with the author(s) at this stage,
and circulation of a work in progress in this series
does not prejudice its later publication.
Comments to authors are welcome.Background: Children and young people with Down's syndrome (DS) present with deficits in expressive speech and language, accompanied by strengths in vocabulary
comprehension compared to nonverbal mental age. Speech intelligibility is particularly impaired, but whether speech is delayed or disordered is a controversial
topic. Most studies suggest a delay, but no studies explore the relationship between cognitive or language skills and intelligibility. This study sought to determine
whether severity of speech disorder correlates with language and cognitive level and to describe the types of errors, developmental or non-developmental, that occur in
the speech of children and adolescents with DS.
Methods & Procedures: 15 children and adolescents with DS (aged 10 to 18) were recruited. Participants completed a battery of standardised speech, language and cognitive assessments. The phonology assessment was subject to process analyses. Results from each test were correlated to determine relationships. Outcome & Results: People with DS present with deficits in receptive and expressive
language that is not wholly accounted for by their cognitive delay. Receptive vocabulary is a strength in comparison to language skills, but it was unclear whether
it is more advanced compared to non-verbal cognitive skills. The majority of speech errors were developmental in nature but all of the children with DS showed at least
one atypical or non-developmental speech error.Conclusions: Children with DS present with speech disorders characterised by (often unusual) atypical errors alongside many developmental errors. Lack of correlation between speech and cognition or language suggests that the speech disorder in Down's syndrome is not simply due to cognitive delay.caslpub155pubWP-1
The use of electropalatography in the treatment of speech disorders in children with Down Syndrome: a randomised controlled trial
This research was supported by a grant from the UK Medical Research Council (G0401388)Background: Electropalatography (EPG) records details of the location and timing of tongue contacts with the hard palate during speech. It has been effective in treating articulation disorders that have failed to respond to conventional therapy approaches but, until now, its use with children and adolescents with intellectual/learning disabilities and speech disorders has been limited. Aims: This study aimed to evaluate the usefulness of EPG in the treatment of speech production difficulties in children and adolescents with Down syndrome (DS) aged 8-18 years. Methods: Twenty-seven children with DS were assessed on a range of cognitive and speech and language measures and underwent additional EPG assessment. Participants were randomly allocated to one of three age-matched groups receiving either EPG therapy, EPG-informed conventional therapy or ‘treatment as usual’ over a 12 week period. The speech of all children was assessed before therapy using the Diagnostic Evaluation of Articulation and Phonology (DEAP: Dodd et al. 2002) and re-assessed immediately post- and 3- and 6-month post-intervention to measure percent consonants correct (PCC). EPG recordings were made of the DEAP assessment items at all time-points. Percent intelligibility was also calculated using the Children’s Speech Intelligibility Measure (CSIM: Wilcox and Morris 1999). Results: Gains in accuracy of production immediately post-therapy, as measured by PCC, were seen for all groups. Reassessment at 3- and 6-month post-therapy revealed that those who had received therapy based directly on EPG visual feedback were more likely to maintain and improve on these gains compared to the other groups. Statistical testing showed significant differences between groups in DEAP scores across time-points although the majority did not survive post hoc evaluation. Intelligibility across time-points, as measured by CSIM, was also highly variable within and between the three groups, but despite significant correlations between DEAP and CSIM at all time-points, no statistically significant group differences emerged. Conclusions and implications: EPG was an effective intervention tool for improving speech production in many participants. This may be because it capitalizes on the relative strength of visual over auditory processing in this client group. The findings would seem to warrant an increased focus on addressing speech production difficulties in current therapyMedical Research Council. Grant Number: G0401388casl54pub5392pub
Модернизация схемы маршрутизации сети передачи данных Красноярской железной дороги на примере протокола OSPF
Decrease in Incidence of Colorectal Cancer Among Individuals 50 Years or Older After Recommendations for Population-based Screening
BACKGROUND & AIMS: The incidence of colorectal cancer (CRC) in the United States is increasing among adults younger than 50 years, but incidence has decreased among older populations after population-based screening was recommended in the late 1980s. Blacks have higher incidence than whites. These patterns have prompted suggestions to lower the screening age for average-risk populations or in blacks. At the same time, there has been controversy over whether reductions in CRC incidence can be attributed to screening. We examined age-related and race-related differences in CRC incidence during a 40-year time period.
METHODS: We determined the age-standardized incidence of CRC from 1975 through 2013 by using the population-based Surveillance, Epidemiology, and End Results (SEER) program of cancer registries. We calculated incidence for 5-year age categories (20-24 years through 80-84 years and 85 years or older) for different time periods (1975-1979, 1980-1984, 1985-1989, 1990-1994, 1995-1999, 2000-2004, 2005-2009, and 2010-2013), tumor subsite (proximal colon, descending colon, and rectum), and stages at diagnosis (localized, regional, and distant). Analyses were stratified by race (white vs black).
RESULTS: There were 450,682 incident cases of CRC reported to the SEER registries during the entire period (1975-2013). Overall incidence was 75.5/100,000 white persons and 83.6/100,000 black persons. CRC incidence peaked during 1980 through 1989 and began to decrease in 1990. In whites and blacks, the decreases in incidence between the time periods of 1980-1984 and 2010-2013 were limited to the screening-age population (ages 50 years or older). Between these time periods, there was 40% decrease in incidence among whites compared with 26% decrease in incidence among blacks. Decreases in incidence were greater for cancers of the distal colon and rectum, and reductions in these cancers were greater among whites than blacks. CRC incidence among persons younger than 50 years decreased slightly between 1975-1979 and 1990. However, among persons 20-49 years old, CRC incidence increased from 8.3/100,000 persons in 1990-1994 to 11.4/100,000 persons in 2010-2013; incidence rates in younger adults were similar for whites and blacks.
CONCLUSIONS: On the basis of an analysis of the SEER cancer registries from 1975 through 2013, CRC incidence decreased only among individuals 50 years or older between the time periods of 1980-1984 and 2010-2013. Incidence increased modestly among individuals 20-49 years old between the time periods of 1990-1994 and 2010-2013. The decision of whether to recommend screening for younger populations requires a formal analysis of risks and benefits. Our observed trends provide compelling evidence that screening has had an important role in reducing CRC incidence
TP53 mutant MDM2-amplified cell lines selected for resistance to MDM2-p53 binding antagonists retain sensitivity to ionizing radiation
Non-genotoxic reactivation of the p53 pathway by MDM2-p53 binding antagonists is an attractive treatment strategy for wild-type TP53 cancers. To determine how resistance to MDM2/p53 binding antagonists might develop, SJSA-1 and NGP cells were exposed to growth inhibitory concentrations of chemically distinct MDM2 inhibitors, Nutlin-3 and MI-63, and clonal resistant cell lines generated. The p53 mediated responses of parental and resistant cell lines were compared. In contrast to the parental cell lines, p53 activation by Nutlin-3, MI-63 or ionizing radiation was not observed in either the SJSA-1 or the NGP derived cell lines. An identical TP53 mutation was subsequently identified in both of the SJSA-1 resistant lines, whilst one out of three identified mutations was common to both NGP derived lines. Mutation specific PCR revealed these mutations were present in parental SJSA-1 and NGP cell populations at a low frequency. Despite cross-resistance to a broad panel of MDM2/p53 binding antagonists, these MDM2-amplified and TP53 mutant cell lines remained sensitive to ionizing radiation (IR). These results indicate that MDM2/p53 binding antagonists will select for p53 mutations present in tumours at a low frequency at diagnosis, leading to resistance, but such tumours may nevertheless remain responsive to alternative therapies, including IR
Diaryl- and triaryl-pyrrole derivatives:Inhibitors of the MDM2-p53 and MDMX-p53 protein-protein interactions
Screening identified 2-(3-((4,6-dioxo-2-thioxotetrahydropyrimidin-5(2H)-ylidene)methyl)-2,5-dimethyl-1H-pyrrol-1-yl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile as an MDM2–p53 inhibitor (IC(50) = 12.3 μM). MDM2–p53 and MDMX–p53 activity was seen for 5-((1-(4-chlorophenyl)-2,5-diphenyl-1H-pyrrol-3-yl)methylene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione (MDM2 IC(50) = 0.11 μM; MDMX IC(50) = 4.2 μM) and 5-((1-(4-nitrophenyl)-2,5-diphenyl-1H-pyrrol-3-yl)methylene)pyrimidine-2,4,6(1H,3H,5H)-trione (MDM2 IC(50) = 0.15 μM; MDMX IC(50) = 4.2 μM), and cellular activity consistent with p53 activation in MDM2 amplified cells. Further SAR studies demonstrated the requirement for the triarylpyrrole moiety for MDMX–p53 activity but not for MDM2–p53 inhibition
Identification of a novel ligand for the ATAD2 bromodomain with selectivity over BRD4 through a fragment growing approach
Structure-guided expansion of a fragment hit for the ATAD2 bromodomain enabled improvement in ATAD2 inhibition and selectivity over BRD4.</p
EyeG2P: an automated variant filtering approach improves efficiency of diagnostic genomic testing for inherited ophthalmic disorders
BACKGROUND: Genomic variant prioritisation is one of the most significant bottlenecks to mainstream genomic testing in healthcare. Tools to improve precision while ensuring high recall are critical to successful mainstream clinical genomic testing, in particular for whole genome sequencing where millions of variants must be considered for each patient. METHODS: We developed EyeG2P, a publicly available database and web application using the Ensembl Variant Effect Predictor. EyeG2P is tailored for efficient variant prioritisation for individuals with inherited ophthalmic conditions. We assessed the sensitivity of EyeG2P in 1234 individuals with a broad range of eye conditions who had previously received a confirmed molecular diagnosis through routine genomic diagnostic approaches. For a prospective cohort of 83 individuals, we assessed the precision of EyeG2P in comparison with routine diagnostic approaches. For 10 additional individuals, we assessed the utility of EyeG2P for whole genome analysis. RESULTS: EyeG2P had 99.5% sensitivity for genomic variants previously identified as clinically relevant through routine diagnostic analysis (n=1234 individuals). Prospectively, EyeG2P enabled a significant increase in precision (35% on average) in comparison with routine testing strategies (p<0.001). We demonstrate that incorporation of EyeG2P into whole genome sequencing analysis strategies can reduce the number of variants for analysis to six variants, on average, while maintaining high diagnostic yield. CONCLUSION: Automated filtering of genomic variants through EyeG2P can increase the efficiency of diagnostic testing for individuals with a broad range of inherited ophthalmic disorders