MetaHD: A multivariate meta-analysis model for metabolomics data.

MOTIVATION: Meta-analysis methods widely-used for combining metabolomics data do not account for correlation between metabolites or missing values. Within- and between-study variability are also often overlooked. These can give results with inferior statistical properties, leading to misidentification of biomarkers. RESULTS: We propose a multivariate meta-analysis model for high-dimensional metabolomics data (MetaHD), which accommodates the correlation between metabolites, within- and between-study variances, and missing values. MetaHD can be used for integrating and collectively analysing individual-level metabolomics data generated from multiple studies as well as for combining summary estimates. We show that MetaHD leads to lower root mean square error compared to the existing approaches. Furthermore, we demonstrate that MetaHD, which exploits the borrowing strength between metabolites, could be particularly useful in the presence of missing data compared to univariate meta-analysis methods, which can return biased estimates in the presence of data missing at random. AVAILABILITY AND IMPLEMENTATION: The MetaHD R package can be downloaded through Comprehensive R Archive Network (CRAN) repository. A detailed vignette with example datasets and code to prepare data and analyses are available on https://bookdown.org/a2delivera/MetaHD/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Extra virgin olive oil improves HDL lipid fraction but not HDL-mediated cholesterol efflux capacity: a double-blind, randomised, controlled, cross-over study (OLIVAUS).

Olive oil (OO) polyphenols have been shown to improve HDL anti-atherogenic function, thus demonstrating beneficial effects against cardiovascular risk factors. The aim of the present study was to investigate the effect of extra virgin high polyphenol olive oil (HPOO) v. low polyphenol olive oil (LPOO) on the capacity of HDL to promote cholesterol efflux in healthy adults. In a double-blind, randomised cross-over trial, fifty participants (aged 38·5 (sd 13·9) years, 66 % females) were supplemented with a daily dose (60 ml) of HPOO (320 mg/kg polyphenols) or LPOO (86 mg/kg polyphenols) for 3 weeks. Following a 2-week washout period, participants crossed over to the alternate treatment. Serum HDL-cholesterol efflux capacity, circulating lipids (i.e. total cholesterol, TAG, HDL, LDL) and anthropometrics were measured at baseline and follow-up. No significant between-group differences were observed. Furthermore, no significant changes in HDL-cholesterol efflux were found within either the LPOO and HPOO treatment arms; mean changes were 0·54 % (95 % CI (0·29, 1·37)) and 0·10 % (95 % CI (0·74, 0·94)), respectively. Serum HDL increased significantly after LPOO and HPOO intake by 0·13 mmol/l (95 % CI (0·04, 0·22)) and 0·10 mmol/l (95 % CI (0·02, 0·19)), respectively. A small but significant increase in LDL of 0·14 mmol/l (95 % CI (0·001, 0·28)) was observed following the HPOO intervention. Our results suggest that additional research is warranted to further understand the effect of OO with different phenolic content on mechanisms of cholesterol efflux via different pathways in multi-ethnic populations with diverse diets.

Prediction of clinical anxious and depressive problems in mid childhood amongst temperamentally inhibited preschool children: a population study.

Shy/inhibited young children are at risk for internalising difficulties; however, for many, this temperamental style does not result in mental health problems. This study followed a population-based sample of temperamentally inhibited preschool children into mid childhood to explore the aetiology of clinical-level anxious and depressive problems. Amongst inhibited preschool children, we aimed to predict each of clinical child anxiety and depressive problems in mid childhood from a broad range of potential risks (demographics, traumatic events and broader recent stressors, parents' well-being, and parenting practices). This study is based on data from a wider population trial of Cool Little Kids that recruited a representative sample of inhibited preschool children enrolled in their year before starting school. In 2011-2012, an inhibition screen was universally distributed to parents of children in their year before school (age 4 years) across eight diverse government areas in Melbourne, Australia. Participants were 545 parents of inhibited preschoolers (78% uptake, 545/703) who were followed to mid childhood (three annual waves 2015-2017, age 7-10 years) with 84% retention (456/545). Parents completed questionnaires spanning child ages 4-10 years, along with diagnostic interviews for child anxiety. Children also completed questionnaires in mid childhood. The questionnaires encompassed a variety of potential risks including sociodemographics, traumatic events, recent life stressors, parent wellbeing and parenting practices. In mid childhood, 57% (246/430) of inhibited preschoolers had a clinical level of anxiety problems while 22% (95/432) had depressive problems (by one or more sources). The aetiology analyses highlighted parent distress and parenting practices (overinvolved/protective, harsh discipline) as key predictors of inhibited preschoolers' internalising problems by mid childhood. Some high-risk families may not have participated. Child depression was not assessed with a diagnostic interview. The measures did not include every possible risk factor. The findings lend support to parenting programs for shy/inhibited young children that aim to prevent the development of anxiety and depression as they grow.

Follow-up of the Cool Little Kids translational trial into middle childhood.

BACKGROUND: Public health advocates have highlighted internalising problems as a leading cause of global burden of disease. Internalising problems (anxiety/depression) affect up to 20% of school-age children and can impact peer relations, school engagement and later employment and mortality. This translational trial aimed to determine whether a selective/indicated parenting group programme to prevent internalising distress in shy/inhibited preschool children had sustained effects in middle childhood. Translational design aspects were a brief parent-report screening tool for child inhibition offered universally across the population via preschools in the year before school, followed by an invitation to parents of all inhibited children to attend the parenting programme at venues in their local community. METHODS: Design of the study was a randomised controlled trial. The setting was 307 preschool services across eight socioeconomically diverse government areas in Melbourne, Australia. Participants were 545 parents of inhibited four-year-old children of which 456 (84%) were retained during middle childhood (age of seven to 10 years). Early intervention was the Cool Little Kids parenting group programme, and control was 'usual care' access to available support services in the community. Primary outcomes were child anxiety and depression symptoms (parent and child report) and DSM-IV anxiety disorders (assessor masked). Secondary outcomes were parenting practices and parent mental health. RESULTS: There was no significant difference in anxiety disorders between the intervention and control group during the three annual follow-ups of the cohort in middle childhood (2015 43% vs. 41%, 2016 40% vs. 36%, 2017 27% vs. 30%, respectively; p's > .05). There were also no significant differences in child anxiety or depression symptoms (by child or parent report), parenting practices or parent mental health, between the intervention and control group during middle childhood. However, a priori interaction tests suggested that for children with anxious parents, early intervention attenuated risk for middle childhood internalising problems. CONCLUSIONS: An issue for population translation is low levels of parent engagement in preventive interventions. Initial effects of the Cool Little Kids parenting group programme in reducing shy/inhibited preschool children's internalising distress at school entry dissipated over time, perhaps due to low engagement. Future translational research on early prevention of internalising problems could benefit from screening preschool children in the population at higher risk (combining temperamental inhibition and parent distress) and incorporating motivational techniques to facilitate family engagement. Trial registration ISRCTN30996662 http://www.isrctn.com/ISRCTN30996662.

Behaviour change interventions to increase physical activity in hospitalised patients: a systematic review, meta-analysis and meta-regression.

BACKGROUND: Low physical activity levels are a major problem for people in hospital and are associated with adverse outcomes. OBJECTIVE: This systematic review, meta-analysis and meta-regression aimed to determine the effect of behaviour change interventions on physical activity levels in hospitalised patients. METHODS: Randomised controlled trials of behaviour change interventions to increase physical activity in hospitalised patients were selected from a database search, supplemented by reference list checking and citation tracking. Data were synthesised with random-effects meta-analyses and meta-regression analyses, applying Grades of Recommendation, Assessment, Development and Evaluation criteria. The primary outcome was objectively measured physical activity. Secondary measures were patient-related outcomes (e.g. mobility), service level outcomes (e.g. length of stay), adverse events and patient satisfaction. RESULTS: Twenty randomised controlled trials of behaviour change interventions involving 2,568 participants (weighted mean age 67 years) included six trials with a high risk of bias. There was moderate-certainty evidence that behaviour change interventions increased physical activity levels (SMD 0.34, 95% CI 0.14-0.55). Findings in relation to mobility and length of stay were inconclusive. Adverse events were poorly reported. Meta-regression found behaviour change techniques of goal setting (SMD 0.29, 95% CI 0.05-0.53) and feedback (excluding high risk of bias trials) (SMD 0.35, 95% CI 0.11-0.60) were independently associated with increased physical activity. CONCLUSIONS: Targeted behaviour change interventions were associated with increases in physical activity in hospitalised patients. The trials in this review were inconclusive in relation to the patient-related or health service benefits of increasing physical activity in hospital.

Cool Little Kids translational trial to prevent internalising: two-year outcomes and prediction of parent engagement.

BACKGROUND: The aim was to determine outcomes in the first year of school of a population-delivered parenting program to prevent internalising problems in temperamentally inhibited preschool children and predictors of engagement in parenting groups. METHOD: Design: Randomised controlled trial. SETTING: 307 preschool services across eight socio-economically diverse government areas in Melbourne, Australia. PARTICIPANTS: 545 parents of inhibited 4-year-old children; 469 (86%) retained at two-year follow-up. INTERVENTION: Cool Little Kids program. Primary outcomes were child internalising symptoms and anxiety disorders. Secondary outcomes were parenting, parent well-being and engagement. Trial registration ISRCTN30996662 http://www.isrctn.com/ISRCTN30996662. RESULTS: In the first year of school (M (SD) age 6.7 (0.4) years), child anxiety symptoms were reduced in the intervention versus control arm (PAS-R M (SD): total 36.2 (17.2) versus 39.4 (18.5); adjusted difference -3.26, 95% CI -6.46 to -0.05, p = .047; specific fears 9.1 (6.2) versus 10.7 (6.8), adjusted difference -1.53; 95% CI -2.69 to -0.38, p = .009). However, there was little difference in broader child internalising (CMFWQ M (SD): 2.2 (0.5) versus 2.3 (0.6); adjusted difference -0.03, 95% CI -0.13 to 0.06, p = .489) or anxiety disorders (37.6% vs. 42.6%; adjusted OR 0.79, 95% CI 0.53 to 1.18, p = .242). Lower income, younger mothers, less educated and more culturally diverse fathers engaged less with the intervention. Continued skills practice was less frequent for parents of girls and in advantaged neighbourhoods. CONCLUSIONS: There were population effects of Cool Little Kids in the first year of school for anxiety symptoms but not disorders. Considering motivation techniques to engage subgroups of families would be helpful in translation research.

Tree pollen exposure is associated with reduced lung function in children.

BACKGROUND: Allergic disease is a recognized global epidemic and a significant cause of ill health and poor quality of life. The prevalence of pollen allergy is high throughout the world, and pollen exposure itself plays a role in emergency department presentations and hospitalizations for asthma. Lung function and airway inflammation are important measures of asthma activity and control. OBJECTIVE: To examine associations between exposure to multiple pollen types and lung function and markers of airway inflammation at 8 and 14 years of age, and to explore potential modification by residential greenness. METHODS: A cohort of high-risk children living in Sydney, Australia had spirometry and fractional exhaled nitric oxide (FeNO) measured at 8 and 14 years of age. Ambient pollen concentration on the day of lung function measurement and up to three days prior was used as the exposure measure. Residential greenness was derived from satellite imagery. We modelled the association between six pollen types and lung function and FeNO. We also assessed modifying effects of residential greenness. RESULTS: Casuarina, cypress and Pinus pollen in the air the day before measurement and 3 days prior respectively, were associated with reduced lung function in 8-year-olds. The pollen exposures were associated with decreases in FEV1 and FVC; however, the FEV1 /FVC ratio was not affected. Effect modification by greenness was not observed due to loss of power. CONCLUSIONS & CLINICAL RELEVANCE: Airborne tree pollen of cypress, Casuarina and Pinus and not grass in some regions may be detrimental to childhood lung function.

Body image in older, inpatient women and the relationship to BMI, anxiety, depression, and other sociodemographic factors.

OBJECTIVES: To determine the prevalence of body image dysfunction in a cohort of older, inpatient women, and to examine any associated health or sociodemographic factors. METHODS: In this cross-sectional, observational study, 50 older women admitted to a subacute hospital completed the Body Shape Questionnaire (BSQ-34), Geriatric Depression Screen (GDS), and Geriatric Anxiety Index (GAI). Additional sociodemographic and health-related data including body mass index (BMI) were collected on all participants. Data were first analysed to determine the prevalence of body image dysfunction. To examine factors significantly associated with body image impairment, partial correlation analyses were initially performed between BSQ-34 score and included variables, followed by stepwise regression analysis undertaken to determine significantly contributing independent variables. RESULTS: Only three out of 50 women displayed body image dysfunction using suggested cut-off scores from the BSQ-34, giving a prevalence rate of only 6%. After controlling for multiple variables however, both higher GDS score and higher BMI were found to be significantly and independently associated with poorer body image, with the strongest association being between higher BSQ-34 score and higher BMI (Spearman rank r = 0.455, P < 0.001). Furthermore, when high BMI and depression occurred together, this association was even greater, accounting for over 50% of the impact on body image scores (P = 0.0001). CONCLUSION: For this small cohort of older, inpatient women, rates of body image dysfunction were low. There did however appear to be an association between poorer body image and higher BMI and depression rates in the group, which may be worth exploring further in less frail, community-dwelling cohorts.

Sustainable waiting time reductions after introducing the STAT model for access and triage: 12-month follow up of a stepped wedge cluster randomised controlled trial.

BACKGROUND: Timely access is a challenge for providers of outpatient and community-based health services, as seen by the often lengthy waiting lists to manage demand. The Specific Timely Appointments for Triage (STAT) model, an alternative approach for managing access and triage, reduced waiting time by 34% in a stepped wedge cluster randomised controlled trial involving 8 services and more than 3000 participants. Follow up periods ranged from 3 to 10 months across the participating services in accordance with the stepped wedge design. This study aimed to determine whether outcomes were sustained for a full 12 months after implementation of the STAT model at each site. METHODS: Routinely collected service data were obtained for a total of 12 months following implementation of the STAT model at each of the 8 services that participated in a stepped wedge cluster randomised controlled trial. The primary outcome was time to first appointment. Secondary outcomes included non-attendance rates, time to second appointment and service use over 12 weeks. Outcomes were compared to pre-intervention data from the original trial, modelled using generalised linear mixed effects models accounting for clustering of sites. RESULTS: A 29% reduction in waiting time could be attributed to STAT over 12 months, compared to 34% in the original trial. A reduction in variability in waiting time was sustained. There were no significant changes in time to second appointment or in the number of missed appointments in the extended follow up period. CONCLUSIONS: STAT is an effective strategy for reducing waiting time in community-based outpatient services. At 12 months, small reductions in the overall effect are apparent, but reductions in variability are sustained, suggesting that people who previously waited the longest benefit most from the STAT model. TRIAL REGISTRATION: This is a 12-month follow up of a stepped wedge cluster randomised controlled trial that was registered with the Australia and New Zealand Clinical Trials Registry ( ACTRN12615001016527 ).

Empirical Shaft Resistance of Driven Piles Penetrating Weak Rock.

In this paper, an empirical relationship between the Unconfined Compressive Strength (UCS) of intact rock and the unit shaft resistance of piles penetrating rock is investigated. A growing number of civil engineering projects are utilizing steel piles driven into rock where a significant portion of the pile capacity is derived from the shaft resistance. Despite the growing number of projects utilizing the technology, little to no guidance is offered in the literature as to how the shaft resistance is to be calculated for such piles. A database has been created for driven piles that penetrate bedrock. The database consists of 42 pile load tests of which a majority are steel H-piles. The friction fatigue model is applied to seven of the pile load tests for which sufficient UCS data exists in order to develop an empirical relation. The focus of this paper is on case histories that include driven pipe piles with at least 2 m penetration into rock.

Pollen exposure at birth and adolescent lung function, and modification by residential greenness.

BACKGROUND: Exposure to high levels of pollen in infancy is a risk factor for allergic respiratory diseases in later childhood, but effects on lung function are not fully understood. We aim to examine associations between grass pollen exposure in the first months of life and lung function at 12 and 18 years, and explore potential modification. METHODS: Using the Melbourne Atopy Cohort Study, a birth cohort of children with a family history of allergic diseases, we modeled the association between cumulative grass pollen exposure up to 3 months after birth, on FEV1 , FVC, and FEV1 /FVC ratio at 12 and 18 years. We also assessed modifying effects of residential greenness levels (derived from satellite imagery), asthma, and early life sensitization to ryegrass. RESULTS: Grass pollen exposure in the first 7 days was associated with a reduction in FEV1 (-15.5 mL; 95% CI: -27.6, -3.3 per doubling of pollen count) and FVC (-20.8 mL; -35.4, -6.1) at 12 years, but not at 18 years. Increase in cumulative grass pollen exposure up to 3 months was negatively associated with FVC at 12 and 18. Exposure to high residential greenness modified the association at 18 years. CONCLUSION: Early exposure to grass pollen was associated with decreased lung function in children and adolescents. Targeted interventions for pollen avoidance strategies that take into account local topography could be implemented alongside other clinical interventions such as immunotherapy.

Scour Damage Detection and Structural Health Monitoring of a Laboratory-Scaled Bridge Using a Vibration Energy Harvesting Device.

A vibration-based bridge scour detection procedure using a cantilever-based piezoelectric energy harvesting device (EHD) is proposed here. This has an advantage over an accelerometer-based method in that potentially, the requirement for a power source can be negated with the only power requirement being the storage and/or transmission of the data. Ideally, this source of power could be fulfilled by the EHD itself, although much research is currently being done to explore this. The open-circuit EHD voltage is used here to detect bridge frequency shifts arising due to scour. Using one EHD attached to the central bridge pier, both scour at the pier of installation and scour at another bridge pier can be detected from the EHD voltage generated during the bridge free-vibration stage, while the harvester is attached to a healthy pier. The method would work best with an initial modal analysis of the bridge structure in order to identify frequencies that may be sensitive to scour. Frequency components corresponding to harmonic loading and electrical interference arising from experiments are removed using the filter bank property of singular spectrum analysis (SSA). These frequencies can then be monitored by using harvested voltage from the energy harvesting device and successfully utilised towards structural health monitoring of a model bridge affected by scour.

A model of access combining triage with initial management reduced waiting time for community outpatient services: a stepped wedge cluster randomised controlled trial.

BACKGROUND: Long waiting times are associated with public community outpatient health services. This trial aimed to determine if a new model of care based on evidence-based strategies that improved patient flow in two small pilot trials could be used to reduce waiting time across a variety of services. The key principle of the Specific Timely Appointments for Triage (STAT) model is that patients are booked directly into protected assessment appointments and triage is combined with initial management as an alternative to a waiting list and triage system. METHODS: A stepped wedge cluster randomised controlled trial was conducted between October 2015 and March 2017, involving 3116 patients at eight sites across a major Australian metropolitan health network. RESULTS: The intervention reduced waiting time to first appointment by 33.8% (IRR = 0.663, 95% CI 0.516 to 0.852, P = 0.001). Median waiting time decreased from a median of 42 days (IQR 19 to 86) in the control period to a median of 24 days (IQR 13 to 48) in the intervention period. A substantial reduction in variability was also noted. The model did not impact on most secondary outcomes, including time to second appointment, likelihood of discharge by 12 weeks and number of appointments provided, but was associated with a small increase in the rate of missed appointments. CONCLUSIONS: Broad-scale implementation of a model of access and triage that combined triage with initial management and actively managed the relationship between supply and demand achieved substantial reductions in waiting time without adversely impacting on other aspects of care. The reductions in waiting time are likely to have been driven, primarily, by substantial reductions for those patients previously considered low priority. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12615001016527 registration date: 29/09/2015.

Powerful differential expression analysis incorporating network topology for next-generation sequencing data.

MOTIVATION: RNA-seq has become the technology of choice for interrogating the transcriptome. However, most methods for RNA-seq differential expression (DE) analysis do not utilize prior knowledge of biological networks to detect DE genes. With the increased availability and quality of biological network databases, methods that can utilize this prior knowledge are needed and will offer biologists with a viable, more powerful alternative when analyzing RNA-seq data. RESULTS: We propose a three-state Markov Random Field (MRF) method that utilizes known biological pathways and interaction to improve sensitivity and specificity and therefore reducing false discovery rates (FDRs) when detecting differentially expressed genes from RNA-seq data. The method requires normalized count data (e.g. in Fragments or Reads Per Kilobase of transcript per Million mapped reads (FPKM/RPKM) format) as its input and it is implemented in an R package pathDESeq available from Github. Simulation studies demonstrate that our method outperforms the two-state MRF model for various sample sizes. Furthermore, for a comparable FDR, it has better sensitivity than DESeq, EBSeq, edgeR and NOISeq. The proposed method also picks more top Gene Ontology terms and KEGG pathways terms when applied to real dataset from colorectal cancer and hepatocellular carcinoma studies, respectively. Overall, these findings clearly highlight the power of our method relative to the existing methods that do not utilize prior knowledge of biological network. AVAILABILITY AND IMPLEMENTATION: As an R package at https://github.com/MalathiSIDona/pathDESeq. TO INSTALL THE PACKAGE TYPE: install_github("MalathiSIDona/pathDESeq",build_vignettes = TRUE). After installation, type vignette("pathDESeq") to access the vignette. CONTACT: a.salim@latrobe.edu.au. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The role of human rhinovirus (HRV) species on asthma exacerbation severity in children and adolescents.

OBJECTIVE: It is recognized that human rhinovirus (HRV) infection is an important factor in asthma exacerbations requiring hospitalization in children. However, previous studies have disagreed on the differential impact of various HRV species. We sought to assess the impact of HRV species on the severity of asthma exacerbations in children and adolescents. We also examined whether the effect of HRV species on severity was modified by age and gender. METHODS: Virus strain was determined for 113 children with HRV detectable at the time of admission for asthma exacerbation. Patient characteristics were collected on admission and exacerbation severity was scored using several validated scales. RESULTS: HRV species by itself was not associated with moderate/severe vs. mild exacerbations. Boys with HRV-C infections were more likely (OR: 3.7, 95% CI: 1.2-13.4) to have a moderate/severe exacerbation than girls with HRV-C (p = 0.04 for interaction term). Higher odds were observed in younger boys (3 years old: OR: 9.1, 95% CI: 1.8-47.1 vs 5 years old: OR: 3.3, 95% CI: 0.9-11.8 vs 7 years old: OR: 1.2, 95% CI: 0.2-6.6). In contrast, children with HRV-C infection and sensitized to pollen during the pollen season were less likely to have moderate/severe exacerbations (p = 0.01 for the interaction term). CONCLUSION: Acute asthma exacerbations are more likely to be moderate/severe in boys under 5 years of age who had HRV-C infection on admission. The opposite was found in children with sensitization to pollen during pollen season.

Translational delivery of Cool Little Kids to prevent child internalising problems: Randomised controlled trial.

OBJECTIVE: To determine whether a population-delivered parenting programme assists in preventing internalising problems at school entry for preschool children at-risk with temperamental inhibition. METHODS: Design: a randomised controlled trial was used. SETTING: the setting was 307 preschool services across eight socioeconomically diverse government areas in Melbourne, Australia. PARTICIPANTS: a total of 545 parents of inhibited 4-year-old children: 498 retained at 1-year follow up. Early intervention: Cool Little Kids parenting group programme was implemented. Primary outcomes: the primary outcomes were child DSM-IV anxiety disorders (assessor blind) and internalising problems. SECONDARY OUTCOMES: the secondary outcomes were parenting practices and parent mental health. RESULTS: At 1-year follow up (mean (standard deviation) age = 5.8 (0.4) years), there was little difference in anxiety disorders between the intervention and control arms (44.2% vs 50.2%; adjusted odds ratio = 0.86, 95% confidence interval = [0.60, 1.25], p = 0.427). Internalising problems were reduced in the intervention arm (Strengths and Difficulties Questionnaire: abnormal - 24.2% vs 33.0%; adjusted odds ratio = 0.56, 95% confidence interval = [0.35, 0.89], p = 0.014; symptoms - mean (standard deviation) = 2.5 (2.0) vs 2.9 (2.2); adjusted mean difference = -0.47, 95% confidence interval = [-0.81, -0.13], p = 0.006). Parents' participation in the intervention was modest (29.4% attended most groups, 20.5% used skills most of the time during the year). A priori interaction tests suggested that for children with anxious parents, the intervention reduced anxiety disorders and internalising symptoms after 1 year. CONCLUSION: Offering Cool Little Kids across the population for inhibited preschoolers does not impact population outcomes after 1 year. Effects may be emerging for inhibited children at highest risk with parent anxiety. Trial outcomes will continue into mid-childhood.

Children with cochlear implants in infancy: predictors of early vocabulary.

BACKGROUND: Language outcomes for children with cochlear implants (CIs) vary widely, even for those implanted before 2 years of age. Identifying the main influencing factors that account for some of the variability is important in order to provide information to guide appropriate clinical and intervention services for young children with CIs. However, there is limited research focusing on the predictors of early vocabulary development for children implanted in infancy. AIMS: To identify significant predictors of vocabulary (12-15 months post-implant) for a sample of 33 children with CIs, the majority implanted between 6 and 10 months of age, drawing on predictors of vocabulary reported for children with normal hearing. Of particular interest was the impact of pre-implant development and use of gestures. METHODS & PROCEDURES: Children with severe to profound hearing loss, and no other known disabilities, were recruited from CI clinics in Australia before receiving their CIs. Subscales from the Bayley Scales-III (receptive and expressive communication, gross and fine motor, and cognition) were used to assess their development at that time. Using the Macarthur-Bates Communicative Development Inventory (Words and Gestures) we documented the children's (1) use of gestures at six data-collection times 3 months apart; and (2) vocabulary at the last three time points. Time since implant and time to consistent use of the CIs were also included as potential predictors. Data were analysed using generalized linear models, assuming a negative binomial response with a log-link function. Stepwise variables selection was followed to retain a smaller number of the covariates. OUTCOMES & RESULTS: A year after implantation, the significant predictors identified for vocabulary were pre-implant receptive communication and early gesture use. Together with fine motor and cognitive skills, these two variables were also significant predictors of vocabulary 3 months later. With maternal education entered into the models, higher vocabulary scores were significantly associated with higher maternal education 12 months post-implantation, but not 15 months. CONCLUSIONS & IMPLICATIONS: Pre-implant abilities are important in explaining some variability in the early vocabulary of infants with CIs, together with their use of early gestures post-implantation. That is, having a non-verbal means to express a concept can assist in their development of oral vocabulary. Identifying strategies to help develop fine motor skills for infants with CIs, and encouraging their use of gestures to communicate their needs/intentions, are likely to be of benefit.

Effects of testosterone treatment on body fat and lean mass in obese men on a hypocaloric diet: a randomised controlled trial.

BACKGROUND: Whether testosterone treatment has benefits on body composition over and above caloric restriction in men is unknown. We hypothesised that testosterone treatment augments diet-induced loss of fat mass and prevents loss of muscle mass. METHODS: We conducted a randomised double-blind, parallel, placebo controlled trial at a tertiary referral centre. A total of 100 obese men (body mass index ≥ 30 kg/m2) with a total testosterone level of or below 12 nmol/L and a median age of 53 years (interquartile range 47-60) receiving 10 weeks of a very low energy diet (VLED) followed by 46 weeks of weight maintenance were randomly assigned at baseline to 56 weeks of 10-weekly intramuscular testosterone undecanoate (n = 49, cases) or matching placebo (n = 51, controls). The main outcome measures were the between-group difference in fat and lean mass by dual-energy X-ray absorptiometry, and visceral fat area (computed tomography). RESULTS: A total of 82 men completed the study. At study end, compared to controls, cases had greater reductions in fat mass, with a mean adjusted between-group difference (MAD) of -2.9 kg (-5.7 to -0.2; P = 0.04), and in visceral fat (MAD -2678 mm2; -5180 to -176; P = 0.04). Although both groups lost the same lean mass following VLED (cases -3.9 kg (-5.3 to -2.6); controls -4.8 kg (-6.2 to -3.5), P = 0.36), cases regained lean mass (3.3 kg (1.9 to 4.7), P < 0.001) during weight maintenance, in contrast to controls (0.8 kg (-0.7 to 2.3), P = 0.29) so that, at study end, cases had an attenuated reduction in lean mass compared to controls (MAD 3.4 kg (1.3 to 5.5), P = 0.002). CONCLUSIONS: While dieting men receiving placebo lost both fat and lean mass, the weight loss with testosterone treatment was almost exclusively due to loss of body fat. TRIAL REGISTRATION: clinicaltrials.gov, identifier NCT01616732 , registration date: June 8, 2012.

Meta-analysis of ratios of sample variances.

When conducting a meta-analysis of standardized mean differences (SMDs), it is common to use Cohen's d, or its variants, that require equal variances in the two arms of each study. While interpretation of these SMDs is simple, this alone should not be used as a justification for assuming equal variances. Until now, researchers have either used an F-test for each individual study or perhaps even conveniently ignored such tools altogether. In this paper, we propose a meta-analysis of ratios of sample variances to assess whether the equality of variances assumptions is justified prior to a meta-analysis of SMDs. Quantile-quantile plots, an omnibus test for equal variances or an overall meta-estimate of the ratio of variances can all be used to formally justify the use of less common methods when evidence of unequal variances is found. The methods in this paper are simple to implement and the validity of the approaches are reinforced by simulation studies and an application to a real data set.

Online processing of sentences containing noun modification in young children with high-functioning autism.

BACKGROUND: There is variability in the language of children with autism, even those who are high functioning. However, little is known about how they process language structures in real time, including how they handle potential ambiguity, and whether they follow referential constraints. Previous research with older autism spectrum disorder (ASD) participants has shown that these individuals can use context to access rapidly the meaning of ambiguous words. The severity of autism has also been shown to influence the speed in which children with ASD access lexical information. AIMS: To understand more about how children with ASD process language in real time (i.e., as it unfolds). The focus was the integration of information and use of referential constraints to identify a referent named in a sentence. METHODS & PROCEDURES: We used an eye-tracking task to compare performance between young, high-functioning children with autism (HFA) and children with typical development (TD). A large sample of 5-9-year-old children (mean age = 6;8 years), 48 with HFA and 56 with TD participated; all were attending mainstream schools. For each item participants were shown a display of four images that differed in two dimensions. Each sentence contained an adjective and noun that restricted the choice from four to two (the target and competitor), followed by a prepositional phrase (e.g., the blue square with dots); this added modifying information to provide a unique description of the target. We calculated looking time at the target, the competitor and the two distractors for each 200 ms time interval as children processed the sentence and looked at the display. Generalized estimating equations were used to carry out repeated-measures analyses on the proportion of looking time to target and competitor and time to fixate to target. OUTCOMES & RESULTS: Children in both groups (HFA and TD) looked at the target and competitor more than at the distractors following the adjective and noun and following the modifying information in the prepositional phrase more at the target. However, the HFA group was significantly slower in both phases and looked proportionally less at the target. Across the sample, IQ and language did not affect the results; however, age and attention had an impact. The older children showed an advantage in processing the information as did the children with higher attention scores. CONCLUSIONS & IMPLICATIONS: The HFA group took longer than the TD group to integrate the disambiguating information provided in the course of processing a sentence and integrate it with the visual information, indicating that for the ASD group incremental processing was not as advanced as for children with ASD, and they were less sensitive to referential conventions. Training for young children with ASD on the use of referential conventions and available contextual clues may be of benefit to them in understanding the language they hear.