EPG providing new insights into complex speech disorders.

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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This series consists of unpublished working- papers. They are not final versions and may be superseded by publication in journal or book form, which should be cited in preference.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

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

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

Wearable activity technology and action-planning (WATAAP) to promote physical activity in cancer survivors: Randomised controlled trial protocol

FUNDAMENTOS/OBJETIVO: Los sobrevivientes de cáncer colorrectal y ginecológico corren riesgo cardiovascular debido a las comorbilidades y al comportamiento sedentario, lo que justifica una intervención factible para aumentar la actividad física. El Enfoque del Proceso de Acción Sanitaria (HAPA) es un marco teórico prometedor para el cambio de comportamiento en materia de salud, y los rastreadores de actividad física que se pueden llevar puestos ofrecen un medio novedoso de autocontrol de la actividad física para los supervivientes de cáncer. MÉTODO: Sesenta y ocho sobrevivientes de cáncer colorrectal y ginecológico serán asignados al azar a grupos de intervención y control de 12 semanas. Los participantes del grupo de intervención recibirán: un Fitbit AltaTM para monitorear la actividad física, sesiones de grupo basadas en HAPA, un folleto y una llamada telefónica de apoyo. Los participantes del grupo de control sólo recibirán el folleto basado en HAPA. La actividad física (utilizando acelerómetros), la presión sanguínea, el IMC y las construcciones HAPA se evaluarán en la línea de base, a las 12 semanas (después de la intervención) y a las 24 semanas (seguimiento). El análisis de los datos utilizará la interacción Grupo x Tiempo de un análisis de Modelo Mixto Lineal General. CONCLUSIONES: Las intervenciones de actividad física que son aceptables y que tienen sólidos fundamentos teóricos son prometedoras para mejorar la salud de los sobrevivientes de cáncer.BACKGROUND/OBJECTIVE: Colorectal and gynecologic cancer survivors are at cardiovascular risk due to comorbidities and sedentary behaviour, warranting a feasible intervention to increase physical activity. The Health Action Process Approach (HAPA) is a promising theoretical framework for health behaviour change, and wearable physical activity trackers offer a novel means of self-monitoring physical activity for cancer survivors. METHOD: Sixty-eight survivors of colorectal and gynecologic cancer will be randomised into 12-week intervention and control groups. Intervention group participants will receive: a Fitbit AltaTM to monitor physical activity, HAPA-based group sessions, booklet, and support phonecall. Participants in the control group will only receive the HAPA-based booklet. Physical activity (using accelerometers), blood pressure, BMI, and HAPA constructs will be assessed at baseline, 12-weeks (post-intervention) and 24-weeks (follow-up). Data analysis will use the Group x Time interaction from a General Linear Mixed Model analysis. CONCLUSIONS: Physical activity interventions that are acceptable and have robust theoretical underpinnings show promise for improving the health of cancer survivors.• The Tonkinson Colorectal Cancer Research. Subvención 57838 • St. John of God Gynecologic Oncology Research Group (Western Australia). AyudapeerReviewe

The wide-field, multiplexed, spectroscopic facility WEAVE: Survey design, overview, and simulated implementation

WEAVE, the new wide-field, massively multiplexed spectroscopic survey facility for the William Herschel Telescope, will see first light in late 2022. WEAVE comprises a new 2-degree field-of-view prime-focus corrector system, a nearly 1000-multiplex fibre positioner, 20 individually deployable 'mini' integral field units (IFUs), and a single large IFU. These fibre systems feed a dual-beam spectrograph covering the wavelength range 366$-$959\,nm at $R\sim5000$, or two shorter ranges at $R\sim20\,000$. After summarising the design and implementation of WEAVE and its data systems, we present the organisation, science drivers and design of a five- to seven-year programme of eight individual surveys to: (i) study our Galaxy's origins by completing Gaia's phase-space information, providing metallicities to its limiting magnitude for $\sim$3 million stars and detailed abundances for $\sim1.5$ million brighter field and open-cluster stars; (ii) survey $\sim0.4$ million Galactic-plane OBA stars, young stellar objects and nearby gas to understand the evolution of young stars and their environments; (iii) perform an extensive spectral survey of white dwarfs; (iv) survey $\sim400$ neutral-hydrogen-selected galaxies with the IFUs; (v) study properties and kinematics of stellar populations and ionised gas in $z<0.5$ cluster galaxies; (vi) survey stellar populations and kinematics in $\sim25\,000$ field galaxies at $0.3\lesssim z \lesssim 0.7$; (vii) study the cosmic evolution of accretion and star formation using $>1$ million spectra of LOFAR-selected radio sources; (viii) trace structures using intergalactic/circumgalactic gas at $z>2$. Finally, we describe the WEAVE Operational Rehearsals using the WEAVE Simulator.Comment: 41 pages, 27 figures, accepted for publication by MNRA

The wide-field, multiplexed, spectroscopic facility WEAVE : survey design, overview, and simulated implementation

Funding for the WEAVE facility has been provided by UKRI STFC, the University of Oxford, NOVA, NWO, Instituto de Astrofísica de Canarias (IAC), the Isaac Newton Group partners (STFC, NWO, and Spain, led by the IAC), INAF, CNRS-INSU, the Observatoire de Paris, Région Île-de-France, CONCYT through INAOE, Konkoly Observatory (CSFK), Max-Planck-Institut für Astronomie (MPIA Heidelberg), Lund University, the Leibniz Institute for Astrophysics Potsdam (AIP), the Swedish Research Council, the European Commission, and the University of Pennsylvania.WEAVE, the new wide-field, massively multiplexed spectroscopic survey facility for the William Herschel Telescope, will see first light in late 2022. WEAVE comprises a new 2-degree field-of-view prime-focus corrector system, a nearly 1000-multiplex fibre positioner, 20 individually deployable 'mini' integral field units (IFUs), and a single large IFU. These fibre systems feed a dual-beam spectrograph covering the wavelength range 366-959 nm at R ∼ 5000, or two shorter ranges at R ∼ 20,000. After summarising the design and implementation of WEAVE and its data systems, we present the organisation, science drivers and design of a five- to seven-year programme of eight individual surveys to: (i) study our Galaxy's origins by completing Gaia's phase-space information, providing metallicities to its limiting magnitude for ∼ 3 million stars and detailed abundances for ∼ 1.5 million brighter field and open-cluster stars; (ii) survey ∼ 0.4 million Galactic-plane OBA stars, young stellar objects and nearby gas to understand the evolution of young stars and their environments; (iii) perform an extensive spectral survey of white dwarfs; (iv) survey  ∼ 400 neutral-hydrogen-selected galaxies with the IFUs; (v) study properties and kinematics of stellar populations and ionised gas in z 1 million spectra of LOFAR-selected radio sources; (viii) trace structures using intergalactic/circumgalactic gas at z > 2. Finally, we describe the WEAVE Operational Rehearsals using the WEAVE Simulator.PostprintPeer reviewe

The Global Alliance for Infections in Surgery : defining a model for antimicrobial stewardship-results from an international cross-sectional survey

Background: Antimicrobial Stewardship Programs (ASPs) have been promoted to optimize antimicrobial usage and patient outcomes, and to reduce the emergence of antimicrobial-resistant organisms. However, the best strategies for an ASP are not definitively established and are likely to vary based on local culture, policy, and routine clinical practice, and probably limited resources in middle-income countries. The aim of this study is to evaluate structures and resources of antimicrobial stewardship teams (ASTs) in surgical departments from different regions of the world. Methods: A cross-sectional web-based survey was conducted in 2016 on 173 physicians who participated in the AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections) project and on 658 international experts in the fields of ASPs, infection control, and infections in surgery. Results: The response rate was 19.4%. One hundred fifty-six (98.7%) participants stated their hospital had a multidisciplinary AST. The median number of physicians working inside the team was five [interquartile range 4-6]. An infectious disease specialist, a microbiologist and an infection control specialist were, respectively, present in 80.1, 76.3, and 67.9% of the ASTs. A surgeon was a component in 59.0% of cases and was significantly more likely to be present in university hospitals (89.5%, p <0.05) compared to community teaching (83.3%) and community hospitals (66.7%). Protocols for pre-operative prophylaxis and for antimicrobial treatment of surgical infections were respectively implemented in 96.2 and 82.3% of the hospitals. The majority of the surgical departments implemented both persuasive and restrictive interventions (72.8%). The most common types of interventions in surgical departments were dissemination of educational materials (62.5%), expert approval (61.0%), audit and feedback (55.1%), educational outreach (53.7%), and compulsory order forms (51.5%). Conclusion: The survey showed a heterogeneous organization of ASPs worldwide, demonstrating the necessity of a multidisciplinary and collaborative approach in the battle against antimicrobial resistance in surgical infections, and the importance of educational efforts towards this goal.Peer reviewe

Combined PI3K and CDK2 inhibition induces cell death and enhances in vivo antitumour activity in colorectal cancer

Background: The phosphatidylinositol-3-kinase/mammalian target of rapamycin (PI3K/mTOR) pathway is commonly deregulated in human cancer, hence many PI3K and mTOR inhibitors have been developed and have now reached clinical trials. Similarly, CDKs have been investigated as cancer drug targets. Methods: We have synthesised and characterised a series of 6-aminopyrimidines identified from a kinase screen that inhibit PI3K and/or mTOR and/or CDK2. Kinase inhibition, tumour cell growth, cell cycle distribution, cytotoxicity and signalling experiments were undertaken in HCT116 and HT29 colorectal cancer cell lines, and in vivo HT29 efficacy studies. Results: 2,6-Diaminopyrimidines with an O4-cyclohexylmethyl substituent and a C-5-nitroso or cyano group (1,2,5) induced cell cycle phase alterations and were growth inhibitory (GI50<20 μM). Compound 1, but not 2 or 5, potently inhibits CDK2 (IC50=0.1 nM) as well as PI3K, and was cytotoxic at growth inhibitory concentrations. Consistent with kinase inhibition data, compound 1 reduced phospho-Rb and phospho-rS6 at GI50 concentrations. Combination of NU6102 (CDK2 inhibitor) and pictilisib (GDC-0941; pan-PI3K inhibitor) resulted in synergistic growth inhibition, and enhanced cytotoxicity in HT29 cells in vitro and HT29 tumour growth inhibition in vivo. Conclusions: These studies identified a novel series of mixed CDK2/PI3K inhibitors and demonstrate that dual targeting of CDK2 and PI3K can result in enhanced antitumour activity