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Background: Clinical trials often include interim analyses of the proportion of participants experiencing an event by a fixed time-point. A pre-specified proportion excluded from a corresponding confidence interval (CI) may lead an independent monitoring committee to recommend stopping the trial. Frequently this cumulative proportion is estimated by the Kaplan-Meier estimator with a Wald approximate CI, which may have coverage issues with small samples., Methods: We reviewed four alternative CI methods for cumulative proportions (Beta Product Confidence Procedure (BPCP), BPCP Mid P, Rothman-Wilson, Thomas-Grunkemeier) and two CI methods for simple proportions (Clopper-Pearson, Wilson). We conducted a simulation study comparing CI methods across true event proportions for 12 scenarios differentiated by sample sizes and censoring patterns. We re-analyzed interim data from A5340, a HIV cure trial considering the proportion of participants experiencing virologic failure., Results: Our simulation study highlights the lower and upper tail error probabilities for each CI method. Across scenarios, we found differences in the performance of lower versus upper bounds. No single method is always preferred. The upper bound of a Wald approximate CI performed reasonably with some error inflation, whereas the lower bound of the BPCP Mid P method performed well. For a trial design similar to A5340, we recommend BPCP Mid P., Conclusions: The design of future single-arm interim analyses of event proportions should consider the most appropriate CI method based on the relevant bound, anticipated sample size and event proportion. Our paper summarizes available methods, demonstrates performance in a simulation study, and includes code for implementation., Competing Interests: Declaration of competing interest The Authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Analyse the linguistic and numerical complexity of COVID-19-related health information communicated from Australian national and state governments and health agencies to national and local early childhood education (ECE) settings., Methods: Publicly available health information (n = 630) was collected from Australian national and state governments and health agencies, and ECE agencies and service providers. A purposive sample of documents (n = 33) from 2020 to 2021 was analysed inductively and deductively combining readability, health numeracy and linguistic analyses and focusing on the most frequent actionable health advice topics., Results: COVID-19 health advice most frequently related to hygiene, distancing and exclusion. Readability scores in 79% (n = 23) of documents were above the recommended grade 6 reading level for the public. Advice was delivered using direct linguistic strategies (n = 288), indirect strategies (n = 73), and frequent mitigating hedges (n = 142). Most numerical concepts were relatively simple, but lacked elaborative features (e.g., analogies) and/or required subjective interpretation., Conclusion: COVID-19 health advice available to the ECE sector included linguistic and numerical information open to mis/interpretation making it difficult to understand and implement., Practice Implications: Combining readability scores with measures of linguistic and numerical complexity offers a more holistic approach to assessing accessibility of health advice and improving health literacy among its recipients., Competing Interests: Declaration of Competing Interest All articles must include a separate file containing a statement declaring any competing interests that relate to any authors. Competing interests are defined as those potential influences that may undermine the objectivity, integrity, or perceived conflict of interest of a publication. Interactions that occur within 5 years before submission date of an article are pertinent., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Randomized trials are an established method to evaluate the causal effects of interventions. Despite concerted efforts to retain all trial participants, some missing outcome data are often inevitable. It is unclear how best to account for missing outcome data in sample size calculations. A standard approach is to inflate the sample size by the inverse of one minus the anticipated dropout probability. However, the performance of this approach in the presence of informative outcome missingness has not been well-studied. We investigate sample size calculation when outcome data are missing at random given the randomized intervention group and fully observed baseline covariates under an inverse probability of response weighted (IPRW) estimating equations approach. Using M-estimation theory, we derive sample size formulas for both individually randomized and cluster randomized trials (CRTs). We illustrate the proposed method by calculating a sample size for a CRT designed to detect a difference in HIV testing strategies under an IPRW approach. We additionally develop an R shiny app to facilitate implementation of the sample size formulas., (© 2023 John Wiley & Sons Ltd.)

Introduction: This study explores the predictive power of macro-structural characteristics on quality rating and improvement system (QRIS) outcomes of Family Day Care (FDC) services in Australia., Methods: The dataset consisted of 441 FDC National Quality Standard (NQS) ratings from all Australian states and territories, with overall ratings of Exceeding NQS, Meeting NQS, Working Towards NQS, or Significant Improvement Required., Results: Multinomial logistic regressions confirmed that management type, community socioeconomic status (SES), level of urbanization, and government jurisdiction explained 6.9 to 19.3% of the variation in QRIS outcomes. Results indicated that lower FDC NQS ratings were more likely for (1) private for-profit vs. not-for-profit; (2) low-SES vs. high-SES area; and (3) regional or remote area vs. metropolitan. State/territory jurisdiction also influenced NQS ratings., Discussion: These findings imply the need for policy attention to inequalities in FDC quality associated with systemic and organizational differences. Greater effort is needed to promote equality and equity in FDC services., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Char, Harrison and Li.)

Acute Coronavirus Disease 2019 symptoms limit daily activities, but little is known about its association with severe acute respiratory syndrome coronavirus 2 viral burden. In this exploratory analysis of placebo recipients in the ACTIV-2/A5401 platform trial, we showed that high anterior nasal RNA levels and detectable plasma RNA were associated with delayed symptom improvement. Clinical Trials Registration. https://clinicaltrials.gov/ct2/show/NCT04518410., Competing Interests: Potential conflicts of interest. L. J. H.: reports grants or contracts from NIH/NIAID 3 UM1 AI068636-16S1 and NIH/NIAID T32 AI007358 (paid to institution). K. W. C.: research funding to the institution from Merck, Sharp & Dohme (paid to institution) and Amgen (research contract with institution), consultant for Pardes Biosciences, honoraria to the author for CME presentations (not-for-profit organization) from International Antiviral Society–USA, participation on a Data Safety Monitoring Board or Advisory Board for University of California, San Francisco (UCSF) (served as Chair of a Safety Monitoring Committee for an investigator-initiated study where the sponsor is UCSF). E. S. D.: receives consulting fees from Gilead Sciences, Merck, and GSK/ViiV and research support through the institution from Gilead Sciences and GSK/ViiV and reports support from NIH, including participation on a Data Safety Monitoring Board or Advisory Board for Gilead and ViiV. D. A. W. has received funding to the institution to support research and honoraria for advisory boards and consulting from Gilead Sciences and grant or contracts from Lilly. J. Z. L. has consulted for AbbVie and received a research grant from Merck. J. J. E. is an ad hoc consultant to GSK/Vir Biotechnology and is data monitoring committee (DMC) chair for Adagio phase III studies. J. S. C. has consulted for Merck and Company and reports a leadership or fiduciary role in other board, society, committee, or advocacy groups as a volunteer for the Board of Directors International Antiviral Society–USA and the Foundation Board, Conference on Retroviruses and Opportunistic Infections. D. M. S. has consulted for Bayer Healthcare, Fluxergy, Kiadis, Linear Therapies, Matrix BioMed, VxBiosciences, Model Medicines, Bayer Pharmaceuticals, and Pharma Holdings; has grants or contracts from NIH (DK131532, AI169609, DA047039, AI036214, AI131385, AI100665, AI126620: funding provided to institution), The James B. Pendleton Charitable Trust, and The James B. Pendleton Charitable Trust John and Mary Tu Foundation, including payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events for Medscape (COVID treatment), American Institute Continuing Medical Education (COVID treatment), and Kiadis; stock or stock options for Model Medicine, Linear Therapies, and Cv Biosciences; and receipt of equipment, materials, drugs, medical writings, gifts, or other services from The James B. Pendleton Charitable Trust. T. H. E. receives consulting fees from Tonix Pharmaceuticals. C. M. reports participation on a Data Safety Monitoring Board for BONE START. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This study assessed the impact of structural characteristics on quality rating and improvement systems (QRIS) outcomes in an Australian national study. Data from the Australian Children's Education and Care Quality Authority (ACECQA) repository of National Quality Standard (NQS) ratings were used to identify long day care services that had improved from Working Towards NQS to Meeting or Exceeding NQS or had no change over two assessments. QRIS outcomes were examined for state/territory jurisdiction, urban-rural location, community socio-economic status, type and size of provider organisation, centre size and stability of centre owner/provider using multinomial logistic regression analyses. Controlling for jurisdiction, results showed that improvement to Meeting NQS was more likely for not-for-profit versus for-profit providers and for large multi-site provider organisations versus small, stand-alone providers. Improvement to Exceeding NQS was also associated with not-for-profit and larger provider organisations, as well as larger versus smaller centres, and centres that had stable ownership., Competing Interests: Conflict of interestThe authors have no conflicts of interest to declare that are relevant to the content of this article. No financial interest or benefit to the authors has arisen from the direct applications of this research., (© The Australian Association for Research in Education, Inc. 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

This national study explored the role of digital technologies in early childhood education and care settings and whether they could contribute to quality improvement as reported by educators and assessors of quality in Australia. In this paper, data from Stage 2 of the Quality Improvement Research Project were used, which comprised 60 Quality Improvement Plans from educators linked with 60 Assessment and Rating reports from the assessors who visited early childhood centres as part of the administration of the National Quality Standards by each of Australia's State and Territory jurisdictions. Bronfenbrenner's ecological systems theory ( Bronfenbrenner, U. (1995). Developmental ecology through space and time: A future perspective. In P. Moen, G. H. Elder, Jr., & K. Lüscher (Eds.), Examining lives in context: Perspectives on the ecology of human development (pp. 619-647). American Psychological Association. 10.1037/10176-018; Bronfenbrenner & Ceci, Bronfenbrenner and Ceci, Psychological Review 101:568-586, 1994) was adopted to facilitate a systemic and dynamic view on the use of digital technologies in these 60 ECEC settings. References (e.g. comments/ suggestions/ examples) made by the educators about the implementation of digital technologies were counted and thematically analysed. Results revealed the strong role new technologies (e.g. documentation and management platforms, tablets, apps, etc.) play in the majority of ECEC settings and especially in relation to three of the seven Quality Areas: Educational programme and practice (Quality Area 1); Collaborative partnerships with families and communities (Quality Area 6) and Governance and leadership (Quality Area 7). Future directions for research are suggested and implications for embracing a more holistic, integrated and broad view on the use of digital technologies are discussed., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2023.)

A safe and just operating space for socioecological systems is a powerful bridging concept in sustainability science. It integrates biophysical earth-system tipping points (ie, thresholds at which small changes can lead to amplifying effects) with social science considerations of distributional equity and justice. Often neglected, however, are the multiple feedback loops between self-identity and planetary boundaries. Environmental degradation can reduce self-identification with nature, leading to decreased pro-environmental behaviours and decreased cooperation with out-groups, further increasing the likelihood of transgressing planetary boundaries. This vicious cycle competes with a virtuous one, where improving environmental quality enhances the integration of nature into self-identity and improves health, thereby facilitating prosocial and pro-environmental behaviour. These behavioural changes can also cascade up to influence social and economic institutions. Given a possible minimum degree of individual self-care to maintain health and prosperity, there would seem to exist an analogous safe and just operating space for self-identity, for which system stewardship for planetary health is crucial., Competing Interests: Declaration of interests All authors institutions were supported by a Natural Environment Research Council grant to conduct this work. THO authored a book with publisher Weidenfeld and Nicholson and has been seconded within the UK Government Office for Science (2022) and UK Department for Food Rural Affairs (2019–21) along with BD and SJM to assist in building systems thinking competencies. ACL has received honoraria or consulting fees from the UN Environment Programme, UK Department for Environment, Food and Rural Affairs, and UK Department for Transport for providing guidance on ambient air quality standards. LJH is co-director and trainer for Leeds Mindfulness Co-operative. NW has received funding for psychological research from the European Research Council, Leverhulme Trust, Sloan Foundation, Templeton World Charity Foundation, Wellcome Trust, and National Health Service. Part of figure 1 was reproduced by permission of Oxfam. Oxfam does not necessarily endorse any text or activities that accompany the materials., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Conventional ecological risk assessment (ERA) predominately evaluates the impact of individual chemical stressors on a limited range of taxa, which are assumed to act as proxies to predict impacts on freshwater ecosystem function. However, it is recognized that this approach has limited ecological relevance. We reviewed the published literature to identify measures that are potential functional indicators of down-the-drain chemical stress, as an approach to building more ecological relevance into ERA. We found wide variation in the use of the term "ecosystem function," and concluded it is important to distinguish between measures of processes and measures of the capacity for processes (i.e., species' functional traits). Here, we present a classification of potential functional indicators and suggest that including indicators more directly connected with processes will improve the detection of impacts on ecosystem functioning. The rate of leaf litter breakdown, oxygen production, carbon dioxide consumption, and biomass production have great potential to be used as functional indicators. However, the limited supporting evidence means that further study is needed before these measures can be fully implemented and interpreted within an ERA and regulatory context. Sensitivity to chemical stress is likely to vary among functional indicators depending on the stressor and ecosystem context. Therefore, we recommend that ERA incorporates a variety of indicators relevant to each aspect of the function of interest, such as a direct measure of a process (e.g., rate of leaf litter breakdown) and a capacity for a process (e.g., functional composition of macroinvertebrates), alongside structural indicators (e.g., taxonomic diversity of macroinvertebrates). Overall, we believe that the consideration of functional indicators can add value to ERA by providing greater ecological relevance, particularly in relation to indirect effects, functional compensation (Box 1), interactions of multiple stressors, and the importance of ecosystem context. Environ Assess Manag 2022;18:1135-1147. © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC)., (© 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).)

Enhancers confer precise spatiotemporal patterns of gene expression in response to developmental and environmental stimuli. Over the last decade, the transcription of enhancer RNAs (eRNAs) - nascent RNAs transcribed from active enhancers - has emerged as a key factor regulating enhancer activity. eRNAs are relatively short-lived RNA species that are transcribed at very high rates but also quickly degraded. Nevertheless, eRNAs are deeply intertwined within enhancer regulatory networks and are implicated in a number of transcriptional control mechanisms. Enhancers show changes in function and sequence over evolutionary time, raising questions about the relationship between enhancer sequences and eRNA function. Moreover, the vast majority of single nucleotide polymorphisms associated with human complex diseases map to the non-coding genome, with causal disease variants enriched within enhancers. In this Primer, we survey the diverse roles played by eRNAs in enhancer-dependent gene expression, evaluating different models for eRNA function. We also explore questions surrounding the genetic conservation of enhancers and how this relates to eRNA function and dysfunction., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

Purpose: Listening to children using age-appropriate techniques supports evidence-based clinical decision-making. In this article, we test the Sound Effects Study Drawing Protocol, an arts-based technique, to support children with speech sound disorder (SSD) to express their views about talking., Method: Participants were 124 Australian children aged 4-5 years in the Sound Effects Study. Their parents and teachers were concerned about their talking, and they were assessed as having SSD on the Diagnostic Evaluation of Articulation and Phonology. Drawings and children's interpretations were elicited then analyzed using the (a) Who Am I? Draw-a-Person Scale and (b) Sound Effects Study Focal Points., Results: Drawings were developmentally typical for 4- to 5-year-olds. The six Sound Effects Study Focal Points were identified across the 124 drawings: body parts and facial expressions, talking and listening, relationships and connection, positivity, negativity, and no talking. Participants portrayed talking and listening as an action requiring mouths and ears represented by symbols (letters, speech bubbles) or as an activity with a variety of people. Children typically portrayed themselves as happy when talking; however, some portrayed negativity and some chose not to draw talking., Conclusions: In keeping with Articles 12 and 13 of the Convention on the Rights of the Child, this research demonstrated that 4- to 5-year-old children with SSD can express their views about talking via drawing. Professionals may use the Sound Effects Study Drawing Protocol as a child-friendly technique to support children to express views to guide holistic, evidence-based, child-centered speech-language pathology practice.

Power calculation for stepped-wedge cluster randomized trials (SW-CRTs) presents unique challenges, beyond those of standard parallel cluster randomized trials, due to the need to consider temporal within cluster correlations and background period effects. To date, power calculation methods specific to SW-CRTs have primarily been developed under a linear model. When the outcome is binary, the use of a linear model corresponds to assessing a prevalence difference; yet trial analysis often employs a nonlinear link function. We propose power calculation methods for cross-sectional SW-CRTs under a logistic model fitted by generalized estimating equations. Firstly, under an exchangeable correlation structure, we show the power based on a logistic model is lower than that from assuming a linear model in the absence of period effects. We then evaluate the impact of background prevalence changes over time on power. To allow the correlation among outcomes in the same cluster to change over time and with treatment status, we generalize the methods to more complex correlation structures. Our simulation studies demonstrate that the proposed power calculation methods perform well with the model-based variance under the true correlation structure and reveal that a working independence structure can result in substantial efficiency loss, while a working exchangeable structure performs well even when the underlying correlation structure deviates from exchangeable. An extension to our methods accounts for variable cluster sizes and reveals that unequal cluster sizes have a modest impact on power. We illustrate the approaches by application to a quality of care improvement trial for acute coronary syndrome., (© 2021 John Wiley & Sons Ltd.)

We evaluated health-related quality of life (QoL) and self-reported incomplete adherence as predictors of early second-line antiretroviral (ART) virological failure (VF). ACTG A5273 study participants completed the ACTG SF-21 measure which has 8 QoL domains. We used exact logistic regression to assess the association of QoL at baseline and week 4 with early VF adjusted for self-reported adherence. Of 500 individuals (51% women, median age 39 years) in this analysis, 79% and 75% self-reported complete adherence (no missing doses in the past month) at weeks 4 and 24, respectively. Early VF was experienced by 7% and more common among those who self-reported incomplete adherence. Participants with low week 4 QoL scores had higher rates of early VF than participants with high scores. After adjusting for self-reported adherence at week 4, VL and CD4 at baseline, cognitive functioning, pain and mental health domains were significantly associated with subsequent early VF. In this post-hoc analysis, poorer QoL adds to self-reported incomplete adherence after 4 weeks of second-line ART in predicting VF at week 24. Evaluation is needed to assess whether individuals with poorer QoL might be targeted for greater support to reduce risk of VF. Trial registration: ClinicalTrials.gov identifier: NCT01352715.

Standard sample size calculation formulas for stepped wedge cluster randomized trials (SW-CRTs) assume that cluster sizes are equal. When cluster sizes vary substantially, ignoring this variation may lead to an under-powered study. We investigate the relative efficiency of a SW-CRT with varying cluster sizes to equal cluster sizes, and derive variance estimators for the intervention effect that account for this variation under a mixed effects model-a commonly used approach for analyzing data from cluster randomized trials. When cluster sizes vary, the power of a SW-CRT depends on the order in which clusters receive the intervention, which is determined through randomization. We first derive a variance formula that corresponds to any particular realization of the randomized sequence and propose efficient algorithms to identify upper and lower bounds of the power. We then obtain an "expected" power based on a first-order approximation to the variance formula, where the expectation is taken with respect to all possible randomization sequences. Finally, we provide a variance formula for more general settings where only the cluster size arithmetic mean and coefficient of variation, instead of exact cluster sizes, are known in the design stage. We evaluate our methods through simulations and illustrate that the average power of a SW-CRT decreases as the variation in cluster sizes increases, and the impact is largest when the number of clusters is small., (© 2019 The International Biometric Society.)

Introduction: The Stanford HIV-1 genotypic resistance interpretation algorithm has changed substantially over its lifetime. In many studies, the algorithm version used is not specified. It is easy to assume that results across versions are comparable, but the effects of version changes on resistance calls are unknown. We evaluate these effects for 20 antiretroviral drugs., Methods: We calculated resistance interpretations for the same 5993 HIV-1 sequences, from participants in AIDS Clinical Trials Group studies, under 14 versions of the Stanford algorithm from 2002 to 2017. Trends over time were assessed using repeated-measures logistic regression. Changes in rule structure and scoring were examined., Results: For most drugs, the proportion of high-level resistance calls on the same sequences was greater using more recent algorithm versions; 16/20 drugs showed significant upward trends. Some drugs, especially tenofovir, had a substantial increase. Only darunavir had a decrease. Algorithm changes impacted calls for subtype C more than B. For intermediate and high-level resistance combined, effects were weaker and more varied. Over time, rules in the Stanford algorithm have become more complex and contain more subrules. The types of rule changes responsible for trends varied widely by drug., Discussion: Reporting the Stanford algorithm version used for resistance analysis is strongly recommended. Caution should be used when comparing results between studies, unless the same version of the algorithm was used. Comparisons using different Stanford versions may be valid for drugs with few changes over time, but for most comparisons, version matters, and for some drugs, the impact is large.

We evaluated health-related quality of life (QoL) in HIV infection participants with virologic failure (VF) on first-line antiretroviral therapy (ART) in 9 resource-limited settings (RLS). ACTG SF-21 was completed by 512 participants at A5273 study entry; 8 domains assessed: general health perceptions (GHP), physical functioning (PF), role functioning (RF), social functioning (SF), cognitive functioning (CF), pain (P), mental health (MH), and energy/fatigue (E/F); each was scored between 0 (worst) to 100 (best). Mean QoL scores ranged from 67 (GHP) to 91 (PF, SF, CF). QoL varied by country; high VL and low CD4 were associated with worse QoL in most domains, except RF (VL only), SF (CD4 only) and CF (neither). Number of comorbidities, BMI and history of AIDS were associated with some domains. Relationships between QoL and VL varied among countries for all domains. The association of worse disease status with worse QoL may reflect low QoL when ART was initiated and/or deterioration associated with VF.

The objective of this study is to examine the trajectory of internalizing problems across middle childhood among a population sample of Australian children, and to understand the timing of explanatory factors related to children's development of internalizing problems, by using multiple-indicator latent growth curve modeling. Participants were children, parents, and teachers in the Longitudinal Study of Australian Children (LSAC) Kindergarten (K) cohort (n = 3,153). Mothers reported on children's internalizing problems at 3 time points (6-7, 8-9, and 10-11 years). Explanatory factors included gender, emotional regulation skills, externalizing problems, peer relationships, parenting behaviors, socioeconomic status, and maternal mental health reported by mothers and teachers at 2 time points (4-5 years and 6-7 years). Growth modeling identified an increasing trajectory of internalizing problems over time. Initial levels were predicted by concurrent (6-7 years) emotional dysregulation, externalizing problems, angry parenting, and maternal mental health problems, as well as earlier (4-5 years) peer problems and maternal mental health. Escalation in internalizing problems was predicted by externalizing problems, peer problems, maternal mental health at 4-5 years, and emotional dysregulation and peer problems at 6-7 years. Girls had both higher initial levels and faster escalation of internalizing problems than boys. The findings provide ecological and developmental evidence and insights for effective intervention. Identifying and addressing early problems with peers may be particularly important to avoid the risk of escalating internalizing problems. Professional development sessions for educators to promote and support children's emotional regulation and peer interaction skills are likely to have a positive impact on children's well-being. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

Objective: We evaluated improvement of quality of life (QoL) after 1 year of second-line antiretroviral therapy (ART) use in resource-limited settings (RLS) among adult men and women, comparing two randomized treatment arms., Design: The AIDS Clinical Trial Group A5273 was a randomized clinical trial of second-line ART comparing lopinavir/ritonavir (LPV/r) + raltegravir with LPV/r + nucleos(t)ide reverse transcriptase inhibitors (NRTIs) in participants failing a non-NRTI-containing regimen at 15 sites in nine RLS. Participants completed the AIDS Clinical Trial Group short-form-21 which has eight QoL domains with a standard score ranging from 0 (worst) to 100 (best)., Methods: Differences in QoL by randomized arm, as well as by demographic and clinical variables, were evaluated by regression models for baseline and week 48 QoL scores fitted using the generalized estimating equations method., Results: A total of 512 individuals (49% men, median age 39 years) were included. A total of 512 and 492 participants had QoL assessments at baseline and week 48, respectively. QoL improved significantly from baseline to week 48 (P < 0.001 for all domains). There was no significant difference between treatment arms for any domain. Individuals with higher viral load and lower CD4 cell count at baseline had lower mean QoL at baseline but larger improvements such that mean QoL was similar at week 48., Conclusion: Improvements in QoL were similar after starting second-line ART of LPV/r combined with either raltegravir or NRTIs in RLS. QoL scores at baseline were lower among participants with worse disease status prior to starting second-line, but after 1 year similar QoL scores were achieved.

Purpose: This study explored how teacher-child relationships change over the early school years, in terms of closeness and conflict, whether these trajectories differ in type and frequency for children with typical development and children with speech and language concern (SLC), and whether the trajectories are associated with school outcomes at 12-13 years., Method: Participants were children, parents and teachers in the Longitudinal Study of Australian Children. Parents identified 2890 children with typical communication and 1442 children with SLC. Teacher-rated teacher-child closeness and conflict were collected biennially over six years. Academic and social-emotional outcomes were reported by teachers and children. Growth mixture modelling was conducted to generate teacher-child relationship trajectories and Wald's chi-square analyses were used to test the association between trajectories and school outcomes at 12-13 years, after controlling for a range of covariates including child's sex, language background, Indigenous status, age and socio-economic position., Result: In both groups, the majority of children had teacher-child relationship trajectories with sustained high closeness and low conflict that predicted positive outcomes at age 12-13, but the SLC group was more at risk of less positive trajectories and poorer school outcomes., Conclusion: Close, less conflicted relationships with teachers may provide a supportive context for later language, literacy and social-emotional development. This study highlights the role of teachers in supporting children in their development of communication and academic skills that will optimise their capacity for freedom of opinions and expression, education and participation, as enshrined in Articles 19, 26 and 27 of the Universal Declaration of Human Rights.

This study explored the longitudinal association between early shared reading and children's later school achievement. We also examined the mediating role of children's academic school readiness and the moderating effect of family socioeconomic status. Data were drawn from the Longitudinal Study of Australian Children ( n = 4,768). Frequency of shared reading and academic school readiness were assessed at the ages of 2-3 and 4-5. School achievement was assessed at age 8-9 via standardized national tests of school literacy and mathematics achievement. Results indicated that early shared reading was associated with children's school achievement directly and indirectly through receptive language and early academic skills. The results also showed that frequency of reading predicts the outcome measures, over and above other home activities such as telling child a story or practicing music. The associations were stronger among low and middle SES groups compared to the high SES group. We conclude that shared reading is uniquely associated to indicators of children's cognitive development such as language and early academic skills as well as children's school achievement. This effect is over and above families' socioeconomic status and other activities that parents do. This may be because books offer unique opportunities to teach children new words and concepts in a systematic way, and this is something that most parents would not be able to do otherwise.

The pork tapeworm, Taenia solium, is prevalent in Uganda although the prevalence has not been determined in all areas of the country. A cross-sectional study, to determine the sero-prevalence of the parasite in pigs kept under rural and urban production settings, was carried out in three Ugandan districts, Masaka, Mukono and Kamuli. Serum samples from 1185 pigs were tested for the presence of T. solium cysticercosis antigen using the HP10 antigen-ELISA (Ag-ELISA) and the ApDia Ag-ELISA assays. Using parallel interpretation of the two tests showed lower levels of observed prevalence of T. solium in rural production settings (10.8%) compared to urban (17.1%). Additionally, Maximum Likelihood Estimation for evaluating assays in the absence of a gold standard, using TAGS on the R platform, estimated the true sero-prevalence to be lower in rural production setting, 0.0% [0.0-3.2%; 95% confidence interval (CI)] than in urban production setting, 12.3% (4.2-77.5% CI). When the sensitivity/specificity (Se/Sp) of the assays were estimated, assuming conditional independence of the tests, HP10 Ag-ELISA was more sensitive and specific [(Se=53.9%; 10.1-100% CI), (Sp=97.0%; 95.9-100% CI)] than the ApDia assay [(Se=20.2%; 1.5-47.7% CI), (Sp=92.2%; 90.5-93.9% CI)]. Subject to parasitological verification, these results indicate there may be a need to implement appropriate control measures for T. solium in the study areas., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Vietnamese is one of the 20 most commonly spoken languages in the world; however, there are no standardised tools to assess Vietnamese children's speech. This study aimed to validate and norm the Vietnamese version of the Intelligibility in Context Scale (ICS-VN). Data were collected from parents of 181 children (aged 2;0-5;11) living in Ha Noi, Northern Viet Nam. The mean ICS-VN score was 4.43 (out of a maximum of 5), indicating that children were 'usually' to 'always' intelligible; however, item-level scores demonstrated significant differences between communication partners. Children with parental concerns about speech and language had significantly lower mean scores than children without parental concerns. Scores also differed by children's age, parents' occupation and mothers' education level but not by sex of child or fathers' education level. The ICS-VN had good psychometric properties indicating it to be a valid tool for use with Vietnamese-speaking children in Northern Viet Nam.

Teachers and peers represent two important dimensions of the classroom social ecology that have important implications for children's social-emotional adjustment. This study examined the combined effects of teacher-child relationships (TCR) and peer relationships for 6-7year-old children on their social-emotional adjustment at 8-9years. The sample was comprised of children and their teachers participating in the Longitudinal Study of Australian Children (n=2857). Teachers reported on TCR, peer relationships, and children's emotional well-being, and children provided self-reported self-concept and school liking during a face-to-face interview. The analytic approach extends previous research by modeling TCR and peer relationships in combination, using cluster analysis to understand the nature of 6-7year-old children's social relationships in the classroom. Five distinct profiles of children were identified: adaptive, teacher-oriented, teacher-child conflict prominent, non-adaptive, and invisible. The adaptive profile had the best outcomes on all three aspects of social-emotional adjustment at age 8-9; the non-adaptive profile had the poorest outcomes, and the invisible group was mid-range. The teacher-oriented and teacher-child conflict prominent groups had mixed outcomes for social-emotional adjustment. Implications for school psychologists and teachers are discussed., (Copyright © 2016 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.)

Background: The discovery of potent and broadly neutralizing antibodies (bNAbs) against human immunodeficiency virus (HIV) has made passive immunization a potential strategy for the prevention and treatment of HIV infection. We sought to determine whether passive administration of VRC01, a bNAb targeting the HIV CD4-binding site, can safely prevent or delay plasma viral rebound after the discontinuation of antiretroviral therapy (ART)., Methods: We conducted two open-label trials (AIDS Clinical Trials Group [ACTG] A5340 and National Institutes of Health [NIH] 15-I-0140) of the safety, side-effect profile, pharmacokinetic properties, and antiviral activity of VRC01 in persons with HIV infection who were undergoing interruption of ART., Results: A total of 24 participants were enrolled, and one serious alcohol-related adverse event occurred. Viral rebound occurred despite plasma VRC01 concentrations greater than 50 μg per milliliter. The median time to rebound was 4 weeks in the A5340 trial and 5.6 weeks in the NIH trial. Study participants were more likely than historical controls to have viral suppression at week 4 (38% vs. 13%, P=0.04 by a two-sided Fisher's exact test in the A5340 trial; and 80% vs. 13%, P<0.001 by a two-sided Fisher's exact test in the NIH trial) but the difference was not significant at week 8. Analyses of virus populations before ART as well as before and after ART interruption showed that VRC01 exerted pressure on rebounding virus, resulting in restriction of recrudescent viruses and selection for preexisting and emerging antibody neutralization-resistant virus., Conclusions: VRC01 slightly delayed plasma viral rebound in the trial participants, as compared with historical controls, but it did not maintain viral suppression by week 8. In the small number of participants enrolled in these trials, no safety concerns were identified with passive immunization with a single bNAb (VRC01). (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTG A5340 and NIH 15-I-0140 ClinicalTrials.gov numbers, NCT02463227 and NCT02471326 .).

A lateral flow assay (LFA) for the diagnosis and monitoring of extraparenchymal neurocysticercosis, has been developed. The assay is based on the use of the monoclonal antibody HP10, and when applied to cerebrospinal fluid, correctly identified 34 cases of active extraparenchymal neurocysticercosis, but was negative with 26 samples from treated and cured neurocysticercosis patients and with 20 samples from unrelated neurological diseases. There was complete agreement between the HP10 Ag-ELISA results and the HP10-LFA. The HP10-LFA thus has utility for diagnosis and treatment of extraparenchymal neurocysticercosis, frequently a more dangerous form of the infection., (Copyright © 2016. Published by Elsevier Inc.)

Unlabelled: Patients with prior virologic failure (VF) are at an increased risk of subsequent failure, emergence of resistance, and death. This analysis identifies outcomes and correlates of VF in a high-risk population., Methods: A5251 was designed to evaluate an enhanced adherence counseling intervention delivered by nurses from a central call site on virologic suppression. Due to slow enrollment, the study was closed prematurely and revised study endpoints were evaluated (week 24 VF (HIV-1 RNA ≥200 copies/ml) and non-perfect adherence (<100% self-reported using both the ACTG adherence questionnaire and visual analog scale (VAS))., Results: Fifty-nine participants were enrolled, 43 (73%) black non-Hispanic and 23 (39%) women. Median prior antiretroviral regimen changes were three and the co-morbidity in this population was higher than typical for HIV clinical trials. At week 24 (n = 41), 24 (59%) failed to reach virologic suppression (HIV-1 RNA <200 copies/ml) and 25 (63%) reported non-perfect adherence. Higher depression (CES-D10) and adverse illness perceptions (IPQ-B) were associated with week 24 non-adherence. Early clinical assessments (week 12 HIV-RNA ≥200 copies/mL and non-perfect adherence) as well as higher depression and adverse illness perceptions were associated with week 24 VF., Discussion: In this high-risk population, the proportion of participants with suboptimal adherence and VF was unacceptably high. Interventions to address this treatment gap are clearly needed. Depression and a higher illness perception score, failure to achieve virologic suppression by week 12, and less than perfect adherence could be used to target individuals for early interventions in treatment-experienced, high-risk individuals at high risk for VF.

Background: For second-line antiretroviral therapy, WHO recommends a boosted protease inhibitor plus nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs). However, concerns about toxicity and cross-resistance motivated a search for regimens that do not contain NRTIs. We aimed to assess whether boosted lopinavir plus raltegravir would be non-inferior to boosted lopinavir plus NRTIs for virological suppression in resource-limited settings., Methods: A5273 was a randomised, open-label, phase 3, non-inferiority study at 15 AIDS Clinical Trials Group (ACTG) research sites in nine resource-limited countries (three sites each in India and South Africa, two each in Malawi and Peru, and one each in Brazil, Kenya, Tanzania, Thailand, and Zimbabwe). Adults with plasma HIV-1 RNA concentrations of at least 1000 copies per mL after at least 24 weeks on a regimen based on a non-NRTI inhibitor were randomly assigned (1:1) to receive oral ritonavir-boosted lopinavir (100 mg ritonavir, 400 mg lopinavir) plus 400 mg raltegravir twice a day (raltegravir group) or to ritonavir-boosted lopinavir plus two or three NRTIs selected from an algorithm (eg, zidovudine after failure with tenofovir and vice versa; NRTI group). Randomised group assignment was done with a computer algorithm concealed to site personnel, and stratified by HIV-1 RNA viral load, CD4 cell count, and intention to use zidovudine, with the groups balanced by each site. The primary endpoint was time to confirmed virological failure (two measurements of HIV-1 RNA viral load >400 copies per mL) at or after week 24 in the intention-to-treat population. Non-inferiority (10% margin) was assessed by comparing the cumulative probability of virological failure by 48 weeks. This trial was registered with ClinicalTrials.gov, NCT01352715., Findings: Between March 13, 2012, and Oct 2, 2013, we randomly assigned 515 participants: 260 to the raltegravir group and 255 to the NRTI group; two participants in the raltegravir group and one in the NRTI group were excluded from analyses because of ineligibility. By the end of follow-up (October, 2014), 96 participants had virological failure (46 in the raltegravir group and 50 in the NRTI group). By 48 weeks, the cumulative probability of virological failure was 10·3% (95% CI 6·5-14·0) in the raltegravir group and 12·4% (8·3-16·5) in the NRTI group, with a weighted difference of -3·4% (-8·4 to 1·5), indicating that raltegravir was non-inferior, but not superior, to NRTIs. 62 (24%) participants in the raltegravir group and 81 (32%) in the NRTI group had grade 3 or higher adverse events; 19 (7%) and 29 (11%), respectively, had serious adverse events. Three participants in each group died, all from HIV-related causes., Interpretation: In settings with extensive NRTI resistance but no available resistance testing, our data support WHO's recommendation for ritonavir-boosted lopinavir plus NRTI for second-line antiretroviral therapy. Ritonavir-boosted lopinavir plus raltegravir is an appropriate alternative, especially if NRTI use is limited by toxicity., Funding: National Institutes of Health., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

We conducted a case-controlled study of the associations of CCR5-Δ32 heterozygosity with human immunodeficiency virus type 1 (HIV-1) reservoir size, lymphocyte activation, and CCR5 expression in 114 CCR5(Δ32/WT) and 177 wild-type CCR5 AIDS Clinical Trials Group participants receiving suppressive antiretroviral therapy. Overall, no significant differences were found between groups for any of these parameters. However, higher levels of CCR5 expression correlated with lower amounts of cell-associated HIV-1 RNA. The relationship between CCR5-Δ32 heterozygosity, CCR5 expression, and markers of HIV-1 persistence is likely to be complex and may be influenced by factors such as the duration of ART., (© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Three hundred forty-three pigs slaughtered and marketed in western Kenya were subjected to lingual examination and HP10 Ag-ELISA for the serological detection of Taenia solium antigen. When estimates were adjusted for the sensitivity and specificity of the diagnostic assays, prevalence of T. solium cysticercosis estimated by lingual exam and HP10 Ag-ELISA was between 34.4% (95% confidence interval (CI) 19.4-49.4%) and 37.6% (95% CI 29.3-45.9%), respectively. All pigs, however, were reported to have passed routine meat inspection. Since T. solium poses a serious threat to public health, these results, if confirmed, indicate that the introduction of control strategies may be appropriate to ensure the safety of pork production in this region.

Unlabelled: Taenia spp. infections, particularly cysticercosis, cause considerable health impacts in endemic countries. Despite previous evidence of spatial clustering in cysticercosis and the role of environmental factors (e.g. temperature and humidity) in the survival of eggs, little research has explored these aspects of Taenia spp., Epidemiology: In addition, there are significant gaps in our understanding of risk factors for infection in humans and pigs. This study aimed to assess the influence of socio-economic, behavioural and environmental variables on human and porcine cysticercosis. A cross-sectional survey for human taeniasis (T. solium and T. saginata), human cysticercosis (T. solium) and pig cysticercosis (T. solium) in 416 households in western Kenya was carried out. These data were linked to questionnaire responses and environmental datasets. Multi-level regression was used to examine the relationships between covariates and human and porcine cysticercosis. The HP10 Ag-ELISA sero-prevalence (suggestive of cysticercosis) was 6.6% for humans (95% CI 5.6%-7.7%), and 17.2% for pigs (95% CI 10.2%-26.4%). Human taeniasis prevalence, based on direct microscopic observation of Taenia spp. eggs (i.e. via microscopy results only) was 0.2% (95% CI 0.05%-0.5%). Presence of Taenia spp. antigen in both humans and pigs was significantly associated with a range of factors, including positive correlations with land cover. The presence of HP10 antigen in humans was correlated (non-linearly) with the proportion of land within a 1 km buffer that was flooding agricultural land and grassland (odds ratio [OR] = 1.09 and 0.998; p = 0.03 and 0.03 for the linear and quadratic terms respectively), gender (OR = 0.58 for males compared to females, p = 0.02), level of education (OR = 0.62 for primary level education versus no formal education, p = 0.09), use of well water for drinking (OR = 2.76 for those who use well water versus those who do not, p = 0.02) and precipitation (OR = 0.998, p = 0.02). Presence of Taenia spp. antigen in pigs was significantly correlated with gender and breeding status of the pig (OR = 10.35 for breeding sows compared to boars, p = 0.01), and the proportion of land within a 1 km buffer that was flooding agricultural land and grassland (OR = 1.04, p = 0.004). These results highlight the role of multiple socio-economic, behavioural and environmental factors in Taenia spp. transmission patterns. Environmental contamination with Taenia spp. eggs is a key issue, with landscape factors influencing presence of Taenia spp. antigens in both pigs and humans.

This longitudinal study examined developmental links between closeness in teacher-child relationships and children's receptive language ability from the end of the preschool years into the early elementary years, while controlling for changes in peer interaction quality and child behavioral functioning. The sample included children and their parents and teachers (N = 4,983) participating in the Longitudinal Study of Australian Children (LSAC) at ages 4-5, 6-7, and 8-9 years (3 waves). Teachers reported on levels of closeness in relationships with individual children. Independent assessments of receptive language were employed. Parents and teachers reported on peer interaction problems and child conduct problems. Results indicated reciprocal associations between close teacher-child relationships and receptive language development above and beyond associations with peer interaction quality and child behavioral functioning. However, the effects were only modest., (PsycINFO Database Record (c) 2015 APA, all rights reserved.)

Background: Quantifying pediatric immunologic recovery by highly active antiretroviral therapy (HAART) initiation at different CD4 percentage (CD4%) and age thresholds may inform decisions about timing of treatment initiation., Methods: HIV-1-infected, HAART-naive children in Europe and the Americas were followed from 2002 through 2009 in PENPACT-1. Data from 162 vertically infected children, with at least World Health Organization "mild" immunosuppression and CD4% <10th percentile, were analyzed for improvement to a normal CD4% (≥10th percentile) within 4 years after HAART initiation. Data from 209 vertically infected children, regardless of immune status, were analyzed for CD4% outcomes at 4 years and viral failure within 4 years., Results: Seventy-two percent of baseline immunosuppressed children recovered to normal within 4 years. Compared with "severe" immunosuppression, more children with "mild" immunosuppression (difference 36%, 95% confidence interval [CI]: 22% to 49%) or "advanced" immunosuppression (difference 20.8%, 95% CI: 5.8% to 35.9%) recovered a normal CD4%. For each 5-year increase in baseline age, the proportion of children achieving a normal CD4% declined by 19% (95% CI: 11% to 27%). Combining baseline CD4% and age effects resulted in >90% recovery when initiating HAART with "mild" immunosuppression at any age or "advanced" immunosuppression at age <3 years. Baseline CD4% effects became greater with increasing age (P = .02). At 4 years, most immunologic benefits were still significant but diminished. Viral failure was highest in infancy (56%) and adolescence (63%)., Conclusions: Initiating HAART at higher CD4% and younger ages maximizes potential for immunologic recovery. Guidelines should weigh immunologic benefits against long-term risks., (Copyright © 2014 by the American Academy of Pediatrics.)

Purpose: The World Report on Disability is an important milestone in the recognition of people with disabilities; however, the Report acknowledges that people with communication difficulties may be underrepresented in estimates of disability. Consequently, this article applies the nine recommendations from the World Report on Disability to supporting children's communication skills., Method: Australia is similar to most Minority World countries since it places high regard on articulate and literate communication. Recent large-scale Australian studies of children with speech, language and communication needs were reviewed to determine prevalence, impact and associated environmental and personal factors. Studies of met and unmet need were reviewed and discussed in relation to legislation and policies., Results: Recent years have seen improvements in the collection of and access to disability data about children's communication, including the involvement of children in research about the impact of communication difficulties on their lives. The prevalence of speech and language impairment in children is high and is associated with poorer educational and social outcomes at school-age. Significant unmet need for services was noted, and there were differences in health, education and disability policies regarding access to services., Conclusions: Updated legislation, policies and practices are needed to more effectively support access to services to support children's communication across health, education and disability sectors. Implications for Rehabilitation There is a high prevalence of speech and language impairment in Australian children. Childhood speech and language impairment (and associated communication disability) can impact educational, social, behavioural and occupational outcomes throughout life. Many Australian children do not have sufficient access to targeted services (including speech-language pathology) to ameliorate the impact of their communication disability. Formulation of a national strategy to support children children's communication is required.

Purpose: To undertake a community (nonclinical) study to describe the speech of preschool children who had been identified by parents/teachers as having difficulties "talking and making speech sounds" and compare the speech characteristics of those who had and had not accessed the services of a speech-language pathologist (SLP)., Method: Stage 1: Parent/teacher concern regarding the speech skills of 1,097 4- to 5-year-old children attending early childhood centers was documented. Stage 2a: One hundred forty-three children who had been identified with concerns were assessed. Stage 2b: Parents returned questionnaires about service access for 109 children., Results: The majority of the 143 children (86.7%) achieved a standard score below the normal range for the percentage of consonants correct (PCC) on the Diagnostic Evaluation of Articulation and Phonology (Dodd, Hua, Crosbie, Holm, & Ozanne, 2002). Consonants produced incorrectly were consistent with the late-8 phonemes ( Shriberg, 1993). Common phonological patterns were fricative simplification (82.5%), cluster simplification (49.0%)/reduction (19.6%), gliding (41.3%), and palatal fronting (15.4%). Interdental lisps on /s/ and /z/ were produced by 39.9% of the children, dentalization of other sibilants by 17.5%, and lateral lisps by 13.3%. Despite parent/teacher concern, only 41/109 children had contact with an SLP. These children were more likely to be unintelligible to strangers, to express distress about their speech, and to have a lower PCC and a smaller consonant inventory compared to the children who had no contact with an SLP., Conclusion: A significant number of preschool-age children with speech sound disorders (SSD) have not had contact with an SLP. These children have mild-severe SSD and would benefit from SLP intervention. Integrated SLP services within early childhood communities would enable earlier identification of SSD and access to intervention to reduce potential educational and social impacts affiliated with SSD.

Significance: The formation and degradation of S-nitrosothiols (SNOs) are important mechanisms of post-translational protein modification and appear to be ubiquitous in biology. These processes play well-characterized roles in eukaryotic cells, including a variety of pathologies and in relation to chronic conditions. We know little of the roles of these processes in pathogenic and other bacteria., Recent Advances: It is clear, mostly from growth and transcriptional studies, that bacteria sense and respond to exogenous SNOs. These responses are phenotypically and mechanistically distinct from the responses of bacteria to nitric oxide (NO) and NO-releasing agents, as well as peroxynitrite. Small SNOs, such as S-nitrosoglutathione (GSNO), are accumulated by bacteria with the result that intracellular S-nitrosoproteins (the 'S-nitrosoproteome') are detectable. Recently, conditions for endogenous SNO formation in enterobacteria have been described., Critical Issues: The propensity of intracellular proteins to form SNOs is presumably constrained by the same rules of selectivity that have been discovered in eukaryotic systems, but is also influenced by uniquely bacterial NO detoxification systems, exemplified by the flavohemoglobin Hmp in enterobacteria and NO reductase of meningococci. Furthermore, the bacterial expression of such proteins impacts upon the formation of SNOs in mammalian hosts., Future Directions: The impairment during bacterial infections of specific SNO events in the mammalian host is of considerable interest in the context of proteins involved in innate immunity and intracellular signalling. In bacteria, numerous mechanisms of S-nitrosothiol degradation have been reported (e.g., GSNO reductase); others are thought to operate, based on consideration of their mammalian counterparts. The nitrosothiols of bacteria and particularly of pathogens warrant more intensive investigation.

Background: The most severe clinical form of neurocysticercosis (NC) occurs when cysticerci are located in the subarachnoid space at the base of the brain (SaB). The diagnosis, monitoring and treatment of NC-SaB, constitutes a severe clinical challenge. Herein we evaluate the potential of the HP10 antigen detection enzyme-linked immunosorbent assay (HP10 Ag-ELISA) in the long term follow-up of NC-SaB cases. Assay performance was compared with that of Magnetic Resonance Imaging (MRI). In addition, the robustness of the HP10 Ag-ELISA was evaluated independently at two different institutions., Methodology/principal Findings: A double-blind prospective cohort trial was conducted involving 38 NC-SaB cases and a total of 108 paired serum and cerebrospinal fluid (CSF) samples taken at intervals of 4 to 8 months for up to 43 months. At each medical visit, results of sera and CSF HP10 Ag-ELISA and MRI obtained at last visit were compared and their accuracy was evaluated retrospectively, considering radiological evolution between appointments. In the long-term follow-up study, HP10 Ag-ELISA had a better agreement than MRI with retrospective radiological evaluation. High reproducibility of HP10 Ag-ELISA between laboratories was also demonstrated., Conclusions: Results reported in this study establish for the first time the usefulness of the comparatively low cost HP10 Ag-ELISA for long term follow-up of NC-SaB patients.

Background: Taenia solium is an important zoonosis in many developing countries. Cysticercosis poses a serious public health risk and leads to economic losses to the pig production industry. Due to scarcity of data on the epidemiology of porcine cysticercosis in Kenya, the present study was conducted to determine the prevalence and risk factors for porcine cysticercosis within Homa Bay district. A cross-sectional survey was carried out in 2010, and a total of 392 pigs were recruited in a household survey, with all being tested by ante-mortem lingual palpation (together with questionnaire data on pig production, occurrence and transmission of porcine cysticercosis, risk factors and awareness of porcine cysticercosis collected from the households from which pigs were sampled). Sufficient serum was collected from 232 of the pigs to be tested for the presence of circulating parasite antigen using a monoclonal antibody-based sandwich enzyme-linked immunosorbent assay (Ag-ELISA)., Results: Seventy six pigs were found positive by the Ag-ELISA (32.8%, 95% C.I. 26.8-39.2%), while by tongue inspection cysticerci were detected in 22/ 392 pigs (5.6% 95% C.I. 3.6-8.4%).The most important risk factor for porcine cysticercosis in the Homa Bay area was for pigs to belong to a farm where latrine use by members of the household was not evident (OR = 1.9, 95% CI = 1.13-2.37)., Conclusion: The present findings indicate that porcine cysticercosis is endemic in Homa Bay District, and that latrine provision, in conjunction with free-range pig keeping contributes significantly to porcine cysticercosis transmission.

Background: in endemic areas, neurocysticercosis appears mainly as a single, large, spherical and non-enhancing intracranial cyst., Case Presentation: an atypical case of neurocysticercosis (NCC) in a French Caucasian, without history of travel to endemic areas, was confirmed by histology and molecular speciation. Imaging was atypical, showing several hook-bearing scolices visible in the cyst, while the serology employed was non-contributary., Conclusions: NCC should be considered when multiple taeniid scolices are observed within the same cystic lesion.

Purpose: To describe a new measure of functional intelligibility, the Intelligibility in Context Scale (ICS), and evaluate its validity, reliability, and sensitivity using 3 clinical measures of severity of speech sound disorder: (a) percentage of phonemes correct (PPC), (b) percentage of consonants correct (PCC), and (c) percentage of vowels correct (PVC)., Method: Speech skills of 120 preschool children (109 with parent-/teacher-identified concern about how they talked and made speech sounds and 11 with no identified concern) were assessed with the Diagnostic Evaluation of Articulation and Phonology (Dodd, Hua, Crosbie, Holm, & Ozanne, 2002). Parents completed the 7-item ICS, which rates the degree to which children's speech is understood by different communication partners (parents, immediate family, extended family, friends, acquaintances, teachers, and strangers) on a 5-point scale., Results: Parents' ratings showed that most children were always (5) or usually (4) understood by parents, immediate family, and teachers, but only sometimes (3) by strangers. Factor analysis confirmed the internal consistency of the ICS items; therefore, ratings were averaged to form an overall intelligibility score. The ICS had high internal reliability (α = .93), sensitivity, and construct validity. Criterion validity was established through significant correlations between the ICS and PPC (r = .54), PCC (r = .54), and PVC (r = .36)., Conclusions: The ICS is a promising new measure of functional intelligibility. These data provide initial support for the ICS as an easily administered, valid, and reliable estimate of preschool children's intelligibility when speaking with people of varying levels of familiarity and authority.

To study diagnostic epitopes within the Taenia solium 8 kDa antigen family, six overlapping synthetic peptides from an 8 kDa family member (Ts8B2) were synthesized and evaluated by ELISA and MABA with sera from patients with neurocysticercosis (NCC), from infected pigs and from rabbits immunized with recombinant Ts8B2 protein. The pre-immune rabbit sera and the Ts8B2 recombinant protein served as negative and positive controls, respectively. A similar analysis was done with the already described antigenic peptides from another member of the 8 kDa family, highly similar to Ts8B2, the CyDA antigen. Surprisingly, neither the Ts8B2 peptides nor the CyDA peptides were recognized by infected human and porcine sera. However, the entire Ts8B2 recombinant, as well as amino and carboxy-terminal halves were recognized by the positive serum samples. The observed lack of recognition of linear Ts8B2 peptides suggests that the principal serological response to the Ts8B2 family is focused on conformational epitopes in contrast to the previously observed antigenicity of the CyDA peptides. This differential antigenicity of 8 kDa family peptides could be related with parasite antigenic variability. The fact that rabbits experimentally immunized with Ts8B2 did make anti-peptide antibodies to peptides Ts8B2-6 and CyDA-6, located in the carboxy-terminal region demonstrated that the Ts8B2 peptides are not intrinsically non-immunogenic., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To examine the longitudinal association between communication impairment (primary or secondary diagnosis) and children's Activities and Participation (International Classification of Functioning, Disability and Health--Children and Youth [ICF-CY]; World Health Organization [WHO], 2007)., Method: Participants were 4,329 children in the Longitudinal Study of Australian Children (LSAC; Australian Institute of Family Studies [AIFS], 2009): 1,041 (24.0%) of these children were identified with communication impairment at 4-5 years of age, and 3,288 (76.0%) of these children were not identified with a communication impairment. At age 7-9 years, Activities and Participation (WHO, 2007) outcomes across 5 ICF-CY domains were provided by (a) teachers (Academic Rating Scales [National Center for Education Statistics (NCES), 2002], Approach to Learning Scale [Gresham & Elliott, 1990], School Progress Scale (AIFS, 2009), Strengths and Difficulties Questionnaire [SDQ; Goodman, 1997], and Student-Teacher Relationship Scale [Pianta, 2001]); (b) parents (School-Age Inventory of Temperament [McClowry, 1995] and SDQ); (c) children (Marsh Self-Description Questionnaire-III [Marsh, 1992], School Liking [Ladd & Price, 1987], and Bullying [Kochenderfer & Ladd, 1997]); and (d) child assessment (Peabody Picture Vocabulary Test--III: Adapted; Rothman, 2003)., Results: Children identified with communication impairment at age 4-5 years performed significantly poorer at age 7-9 years on all outcomes. Parents and teachers reported slower progression in reading, writing, and overall school achievement than peers. Children reported more bullying, poorer peer relationships, and less enjoyment of school than did their peers. Analyses of covariance tests confirmed significant associations between communication impairment and outcomes, over and above the effects of sex, age, Indigenous status, and socioeconomic status., Conclusion: Consideration of the breadth and longevity of Activities and Participation outcomes reveals the potential extent and severity of communication impairment and directs future research and practice.

Speech impairment (speech sound disorder) is a high prevalence condition that responds well to early intervention provided by speech-language pathologists (SLPs). However, not all children in Australia are able to access necessary speech-language pathology services. The aim of this research was to investigate Australian parents' experiences of accessing and engaging in speech-language pathology services for their children with speech impairment. Two studies were conducted to achieve this aim. In Study 1, questionnaires were completed by 109 parents of pre-school children who had been identified with concerns about their speech. Only a third (n = 34, 31.2%) of the parents had previously accessed speech-language pathology services for assessment of their children's speech and just 29 of these (26.6% of the entire sample) reported their children had received intervention. Two thirds (n = 68, 62.4%) of the parents had not sought speech-language pathology services and half of these (n = 35, 32.1% of the entire sample) reported that "services were not needed". There was a small number of parents (n = 7, 6.4%) who had attempted to access services but had been unsuccessful. Parents identified teachers, family, friends, and doctors as important sources of information about their children's speech. In Study 2, interviews were conducted with 13 of the parents to discuss their experiences of speech impairment and service delivery in greater depth. Parents expected that others would make them aware of their child's speech impairment and that they should be able to access speech-language pathology services when required. Consequently, there is a need to raise awareness about speech impairment and speech-language pathology services to ensure appropriate identification, referral, and service provision for children at risk.

Purpose: The purpose of this article was to understand the experience of speech impairment (speech sound disorders) in everyday life as described by children with speech impairment and their communication partners., Method: Interviews were undertaken with 13 preschool children with speech impairment (mild to severe) and 21 significant others (family members and teachers)., Results: A phenomenological analysis of the interview transcripts revealed 2 global themes regarding the experience of living with speech impairment for these children and their families. The first theme encompassed the problems experienced by participants, namely (a) the child's inability to "speak properly," (b) the communication partner's failure to "listen properly," and (c) frustration caused by the speaking and listening problems. The second theme described the solutions participants used to overcome the problems. Solutions included (a) strategies to improve the child's speech accuracy (e.g., home practice, speech-language pathology) and (b) strategies to improve the listener's understanding (e.g., using gestures, repetition). Both short- and long-term solutions were identified., Conclusion: Successful communication is dependent on the skills of speakers and listeners. Intervention with children who experience speech impairment needs to reflect this reciprocity by supporting both the speaker and the listener and by addressing the frustration they experience.