Effect of dialect on phonological analysis.

It is important to understand a child's language background, to ensure appropriate assessment, diagnosis and treatment of speech sound disorders. Singapore is home to various cultures and languages, and local speech norms are needed to provide an accurate reference for assessing phonological disorders in the local population. This study aims to establish normative data and better understand the English phonological development of English-Mandarin bilingual preschoolers in Singapore, aged 3; 6-4; 5 years. The Articulation and Phonology subtests of the Diagnostic Evaluation of Articulation and Phonology - UK were used to collect speech data from 146 preschoolers. Responses were scored against two standards - British Standard English (BSE) and Singapore English (SGE), in terms of speech sound accuracy, and the frequency and type of error patterns present. The effect of language dominance on the children's English phonological abilities was explored. Results showed that the preschoolers' speech sound accuracy increased significantly when scored against SGE versus BSE targets. The number of children identified to be using several error patterns was reduced when SGE targets were used instead of BSE targets. English-dominant children scored significantly higher than their Mandarin-dominant peers on measures of speech sound accuracy. The identification of error patterns also differed between the two groups. These results show that it is important to take dialectal variation and language dominance into account in assessment, to determine if speech characteristics are due to a speech sound disorder or just normal dialectal variations.

Unbound drug concentration in brain homogenate and cerebral spinal fluid at steady state as a surrogate for unbound concentration in brain interstitial fluid.

The objective of the present study was to examine the accuracy of using unbound brain concentration determined by a brain homogenate method (C(ub)), cerebral spinal fluid concentration (C(CSF)), and unbound plasma concentration (C(up)) as a surrogate for brain interstitial fluid concentration determined by brain microdialysis (C(m)). Nine compounds-carbamazepine, citalopram, ganciclovir, metoclopramide, N-desmethylclozapine, quinidine, risperidone, 9-hydroxyrisperidone, and thiopental-were selected, and each was administered as an intravenous bolus (up to 5 mg/kg) followed by a constant intravenous infusion (1-9 mg/kg/h) for 6 h in rats. For eight of the nine compounds, the C(ub)s were within 3-fold of their C(m); thiopental had a C(m) 4-fold of its C(ub). The C(CSF)s of eight of the nine compounds were within 3-fold of their corresponding C(m); 9-hydroxyrisperidone showed a C(CSF) 5-fold of its C(m). The C(up)s of five of the nine compounds were within 3-fold of their C(m); four compounds (ganciclovir, metoclopramide, quinidine, and 9-hydroxyrisperidone) had C(up)s 6- to 14-fold of their C(m). In conclusion, the C(ub) and C(CSF) were within 3-fold of the C(m) for the majority of the compounds tested. The C(up)s were within 3-fold of C(m) for lipophilic non-P-glycoprotein (-P-gp) substrates and greater than 3-fold of C(m) for hydrophilic or P-gp substrates. The present study indicates that the brain homogenate and cerebral spinal fluid methods may be used as surrogate methods to predict brain interstitial fluid concentrations within 3-fold of error in drug discovery and development settings.

Putting Time in Perspective: An Integrated Graduate Medical Education Institutional Dashboard and Report Card.

BACKGROUND: ACGME-I requires sponsoring institutions (SIs) to have systematic oversight of program performance. This was initially carried out through annual review, however, maintaining compliance became a challenge for a large SI like Singapore Health Services (SingHealth) as the number of residency programs grew from 5 to 34 in 3 years. OBJECTIVE: We assessed the impact of quarterly monitoring using a dashboard on graduate medical education (GME) program performance and institutional oversight. METHODS: In 2014, the SingHealth GME Committee (GMEC) approved the dashboard covering 13 indicators with implication on program performance, resident/faculty performance, and finance. Indicators were given color-coded scoring for compliance, borderline compliance, or concern. From annual reporting, periodicity was increased quarterly with reports distributed to program directors, head of department, and academic clinical programs. RESULTS: Since implementation, programs consistently met or exceeded compliance standards in 11 of 13 indicators (84%), with 7 indicators (63%) showing upward trends. Programs with borderline scores in particular quarters showed improvement in subsequent quarters. By 2015, percentage compliance for the 3 dimensions of residents' perspectives were 1 to 2 points higher than the national compliance average. Of 19 programs undergoing ACGME-I accreditation in 2014, only 4 had citations in the foundational requirement. Institutional citations were resolved, with 0 citations in the reaccreditation site visit in 2015. CONCLUSIONS: For a large SI, increased periodicity of program performance reporting from annual to quarterly effectively addressed the gaps in a timely fashion. Institutional performance also improved through the use of quantitative data aligned with institution and national performance indicators.

Tests over time: Evaluating the currency of normative data in a complex multilingual environment.

BACKGROUND: Assessment of oral language skills is challenging in multilingual environments. With language policies promoting increased use of English and reduction of dialectal varieties of languages, rapid changes in language further confound assessment. PURPOSE: This study explores the currency of normative data on an expressive language screening tool in English for English-Mandarin bilingual Singaporean children. METHOD: Spoken language samples in English from 101 pre-school children were compared with those from 481 children in the original data collection in 2002. Scores for expressive vocabulary and morphosyntax were compared for the two main language groups. RESULT: Results indicate that the normative data for English-dominant children are still current. The data for younger Mandarin-dominant children showed improved test scores, indicating improvement in expressive morphosyntax in English. CONCLUSION: English language competency has changed over time for Mandarin-dominant children in Singapore, likely due to the influence of language policy on language use. This is a particular challenge in multilingual environments. Current literature emphasizes the need to develop language assessments specific to populations and language groups for standardized assessments to be valid and reliable. These results demonstrate the need to monitor normative data and characteristics of language over time and to update standardized language assessments accordingly.

Laboratory evaluation of temperature effects on the germination and growth of entomopathogenic fungi and on their pathogenicity to two aphid species.

As part of an approach to select potential mycoinsecticides for aphid biocontrol, we investigated the effects of temperature on the growth, germination and pathogenicity of some hyphomycete fungi. Commercially available mycoinsecticides (based on Beauveria bassiana (Balsamo) Vuillemin and Verticillium lecanii (Zimmermann) Viegas) and other isolates of B bassiana, V lecanii, Metarhizium anisopliae (Metschnikoff) Sorokin and Paecilomyces fumosoroseus (Wize) Brown & Smith were evaluated. The rate of in vitro conidial germination of all isolates was slower at 10 and 15 degrees C than at 20 and 25 degrees C. Similarly, in vitro growth of most isolates was adversely affected at 10 and 15 degrees C. The greatest reduction at 10 degrees C in rates of conidial germination and colony growth, compared with other temperatures, was for M anisopliae isolates. Germination of V lecanii (isolate HRI 1.72) was fastest at 10 degrees C compared with the other fungi. It was also the most pathogenic of three isolates tested against Aphis fabae Scopoli and Myzus persicae Sulzer at 10, 18 and 23 degrees C. Generally, A fabae was more susceptible than M persicae to infection by the fungal isolates tested. A significant interaction between aphid species and temperature indicated that the pathogenic nature of an isolate was dependent not only on the target aphid species but also the temperature conditions of the bioassay. The series of studies, detailed above, allowed a temperature profile to be formed for the different isolates. Verticillium lecanii isolate HRI 1.72 (commercialised as Vertalec) was the most promising isolate selected from results of the series of experiments. Temperature profiles in conjunction with infectivity assays can be useful in selecting appropriate isolates for a particular thermal environment.

AAPS-FDA workshop white paper: microdialysis principles, application and regulatory perspectives.

Many decisions in drug development and medical practice are based on measuring blood concentrations of endogenous and exogenous molecules. Yet most biochemical and pharmacological events take place in the tissues. Also, most drugs with few notable exceptions exert their effects not within the bloodstream, but in defined target tissues into which drugs have to distribute from the central compartment. Assessing tissue drug chemistry has, thus, for long been viewed as a more rational way to provide clinically meaningful data rather than gaining information from blood samples. More specifically, it is often the extracellular (interstitial) tissue space that is most closely related to the site of action (biophase) of the drug. Currently microdialysis (microD) is the only tool available that explicitly provides data on the extracellular space. Although microD as a preclinical and clinical tool has been available for two decades, there is still uncertainty about the use of microD in drug research and development, both from a methodological and a regulatory point of view. In an attempt to reduce this uncertainty and to provide an overview of the principles and applications of microD in preclinical and clinical settings, an AAPS-FDA workshop took place in November 2005 in Nashville, TN, USA. Stakeholders from academia, industry and regulatory agencies presented their views on microD as a tool in drug research and development.