Design and evaluation of a CAL system to support communication development in children with autism

The prevalence of autism in children in the United Kingdom is estimated as one in one hundred (Department of Health, 2012), with higher levels reported in some countries (Srivastava, 2013). These children experience significant problems with the development of language and communication skills. A symbol-based communication system called Picture Exchange Communication System (PECS) is widely used to address this issue and evidence indicates this approach can be effective when administered by trained professionals (Preston and Carter, 2009). Technology appears to offer an alternative way of encouraging non-verbal children with autism to use symbol-based communication to improve social interaction and communication. Therefore, the purpose of the research was to answer the following research questions: 1. Can a Computer Assisted Learning (CAL) system be designed and implemented to support PECS pedagogy for the purpose of improving symbol communication and social interaction in non-verbal children with autism? 2. To what extent could such a system improve the communication and social interaction skills of non-verbal children with autism? The investigation comprised three stages. In Stage 1, a prototype system was developed incorporating a 'virtual tutor' and an RFID-based (radio frequency identification) user interface to support physical symbol selection and placement. In Stage 2, a pilot study focused on classroom learning experiences of eight children using CAPE Version 1. Results provided ‘proof of concept’ and indicated that non-verbal children with autism learned to interact effectively with CAPE. Participants achieved more appropriate symbol selections when a virtual tutor used a synthetic voice compared to a natural voice alternative. Outcomes from the pilot informed the development of a CAPE Version 2. Stage 3 comprised a four-week classroom study involving five non-verbal children with autism. Children, using CAPE Version 2, answered numeracy questions using graphic symbols. Interviews from supporting teachers provided a degree of triangulation with investigator observations and teacher interviews. Stage 3 results suggest that four participants developed their communication skills, one child learned to count, three children improved basic numeracy skills and two children used speech using CAPE version 2, supported by a virtual tutor and a human teacher. This research suggests that non-verbal children with autism can engage positively and productively with PECS using the CAPE approach

Transcriptome profiling reveals significant changes in the gastric muscularis externa with obesity that partially overlap those that occur with idiopathic gastroparesis

BACKGROUND: Gastric emptying is impaired in patients with gastroparesis whereas it is either unchanged or accelerated in obese individuals. The goal of the current study was to identify changes in gene expression in the stomach muscularis that may be contributing to altered gastric motility in idiopathic gastroparesis and obesity. METHODS: Quantitative real time RT-PCR and whole transcriptome sequencing were used to compare the transcriptomes of lean individuals, obese individuals and either lean or obese individuals with idiopathic gastroparesis. RESULTS: Obesity leads to an increase in mRNAs associated with muscle contractility whereas idiopathic gastroparesis leads to a decrease in mRNAs associated with PDGF BB signaling. Both obesity and idiopathic gastroparesis were also associated with similar alterations in pathways associated with inflammation. CONCLUSIONS: Our findings show that obesity and idiopathic gastroparesis result in overlapping but distinct changes in the gastric muscularis transcriptome. Increased expression of mRNAs encoding smooth muscle contractile proteins may be contributing to the increased gastric motility observed in obese subjects, whereas decreased PDGF BB signaling may be contributing to the impaired motility seen in subjects with idiopathic gastroparesis

Gastroparesis is associated with decreased FOXF1 and FOXF2 in humans, and loss of FOXF1 and FOXF2 results in gastroparesis in mice

Background and Aims The transcription factors FOXF1 and FOXF2 have been implicated in the development of the gastrointestinal tract but their role in adults or in gastrointestinal diseases is poorly understood. We have recently shown that expression of serum response factor (SRF), a transcription factor whose activity is modulated by FOXF proteins, is decreased in the stomach muscularis of patients with gastroparesis. The aim of the current study was to determine whether FOXF expression is decreased in gastroparesis patients and whether loss of FOXF1 and/or FOXF2 from adult smooth muscle is sufficient to impair gastric emptying in mice. Methods Full‐thickness stomach biopsy samples were collected from control subjects and from patients with gastroparesis. mRNA was isolated from the muscularis externa, and FOXF mRNA expression levels were determined by quantitative reverse transcriptase (RT)‐PCR. Foxf1 and Foxf2 were knocked out together and separately from smooth muscle cells in adult mice, and the subsequent effect on liquid gastric emptying and contractile protein expression was determined. Key Results Expression of FOXF1 and FOXF2 is decreased in smooth muscle tissue from gastroparesis patients. Knockout of Foxf1 and Foxf2 together, but not alone, from mouse smooth muscle resulted in delayed liquid gastric emptying. Foxf1/2 double knockout mice had decreased expression of smooth muscle contractile proteins, SRF, and myocardin in stomach muscularis. Conclusions and Inferences Our findings suggest that decreased expression of FOXF1 and FOXF2 may be contributing to the impaired gastric emptying seen in gastroparesis patients

Idiopathic gastroparesis is associated with specific transcriptional changes in the gastric muscularis externa

BACKGROUND: The molecular changes that occur in the stomach that are associated with idiopathic gastroparesis are poorly described. The aim of this study was to use quantitative analysis of mRNA expression to identify changes in mRNAs encoding proteins required for the normal motility functions of the stomach. METHODS: Full-thickness stomach biopsy samples were collected from non-diabetic control subjects who exhibited no symptoms of gastroparesis and from patients with idiopathic gastroparesis. mRNA was isolated from the muscularis externa and mRNA expression levels were determined by quantitative reverse transcriptase (RT)-PCR. KEY RESULTS: Smooth muscle tissue from idiopathic gastroparesis patients had decreased expression of mRNAs encoding several contractile proteins, such as MYH11 and MYLK1. Conversely, there was no significant change in mRNAs characteristic of interstitial cells of Cajal (ICCs) such as KIT or ANO1. There was also a significant decrease in mRNA-encoding platelet-derived growth factor receptor α (PDGFRα) and its ligand PDGFB and in Heme oxygenase 1 in idiopathic gastroparesis subjects. In contrast, there was a small increase in mRNA characteristic of neurons. Although there was not an overall change in KIT expression in gastroparesis patients, KIT expression showed a significant correlation with gastric emptying whereas changes in MYLK1, ANO1 and PDGFRα showed weak correlations to the fullness/satiety subscore of patient assessment of upper gastrointestinal disorder-symptom severity index scores. CONCLUSIONS AND INFERENCES: Our findings suggest that idiopathic gastroparesis is associated with altered smooth muscle cell contractile protein expression and loss of PDGFRα+ cells without a significant change in ICCs

The beginning of time? Evidence for catastrophic drought in Baringo in the early nineteenth century

New developments in the collection of palaeo-data over the past two decades have transformed our understanding of climate and environmental history in eastern Africa. This article utilises instrumental and proxy evidence of historical lake-level fluctuations from Baringo and Bogoria, along with other Rift Valley lakes, to document the timing and magnitude of hydroclimate variability at decadal to century time scales since 1750. These data allow us to construct a record of past climate variation not only for the Baringo basin proper, but also across a sizable portion of central and northern Kenya. This record is then set alongside historical evidence, from oral histories gathered amongst the peoples of northern Kenya and the Rift Valley and from contemporary observations recorded by travellers through the region, to offer a reinterpretation of human activity and its relationship to environmental history in the nineteenth century. The results reveal strong evidence of a catastrophic drought in the early nineteenth century, the effects of which radically alters our historical understanding of the character of settlement, mobility and identity within the Baringo–Bogoria basin

Patterns in reduction or cessation of drinking in Australia (2001-2013) and motivation for change

Aims: This paper examines: 1) change over time (2001-2013) in recently reducing or ceasing drinking in the Australian population, and 2) the reasons given for reducing or ceasing drinking in the most recent survey (2013); stratified by sex and age group. Methods: Data are from five waves of the National Drug Strategy Household Survey (N=119,397). Logistic regression models with interaction terms were used to identify a shift in sex or age over time in predicting reduction or cessation of drinking, and to predict motivations for reducing or ceasing drinking by sex and age. Results: Reports of recently reducing the quantity or frequency of drinking increased from 2001 to 2007, and remained stable between 2007 and 2013. There was a steady increase in the number of Australians reporting recently ceasing drinking from 2001 to 2013, with a significant effect for age (younger groups more likely than older groups to cease drinking in the past two waves). Reasons for reducing or ceasing drinking varied by age, with older people more likely to report health reasons, and younger people more likely to report lifestyle reasons or enjoyment. Conclusion: Increases over time in reports of reduction or cessation of drinking due to health, lifestyle, social and enjoyment reasons, suggests that the social position of alcohol in Australia may be shifting, particularly among young people

Response to commentaries: (de)normalization of drinking and its implications for young people, sociality, culture and epidemiology

Commentar

The Concussion Recognition Tool 5th Edition (CRT5): Background and rationale

The Concussion Recognition Tool 5 (CRT5) is the most recent revision of the Pocket Sport Concussion Assessment Tool 2 that was initially introduced by the Concussion in Sport Group in 2005. The CRT5 is designed to assist non-medically trained individuals to recognise the signs and symptoms of possible sport-related concussion and provides guidance for removing an athlete from play/sport and to seek medical attention. This paper presents the development of the CRT5 and highlights the differences between the CRT5 and prior versions of the instrument

Daclatasvir in combination with asunaprevir and beclabuvir for hepatitis C virus genotype 1 infection with compensated cirrhosis

Importance Effective and well-tolerated, interferon-free regimens are needed for treatment of patients with chronic hepatitis C virus (HCV) infection and cirrhosis. Objective All-oral therapy with daclatasvir (nonstructural protein 5A [NS5A] inhibitor), asunaprevir (NS3 protease inhibitor), and beclabuvir (nonnucleoside NS5B inhibitor), with or without ribavirin, was evaluated in patients with HCV genotype 1 infection and compensated cirrhosis. Design, Setting, and Participants The UNITY-2 study was conducted between December 2013 and October 2014 at 49 outpatient sites in the United States, Canada, France, and Australia. Patients were treated for 12 weeks, with 24 weeks of follow-up after completion of treatment. Adult patients with cirrhosis were enrolled in 2 cohorts: HCV treatment-naive or HCV treatment-experienced. Statistical analyses were based on historical controls; there were no internal controls. Interventions All patients received twice-daily treatment with the fixed-dose combination of daclatasvir (30 mg), asunaprevir (200 mg), and beclabuvir (75 mg). In addition, patients within each cohort were stratified according to HCV genotype 1 subtype (1a or 1b) and randomly assigned (1:1) to receive double-blinded weight-based ribavirin (1000-1200 mg/d) or matching placebo. Main Outcomes and Measures Sustained virologic response at posttreatment week 12 (SVR12). Results One hundred twelve patients in the treatment-naive group and 90 patients in the treatment-experienced group were treated and included in the analysis. Enrolled patients were 88% white with a median age of 58 years (treatment-naive group) or 60 years (treatment-experienced group); 74% had genotype 1a infection. SVR12 rates were 98% (97.5% CI, 88.9%-100%) for patients in the treatment-naive group and 93% (97.5% CI, 85.0%-100.0%) for those in the treatment-experienced group when ribavirin was included in the regimen. With the fixed-dose combination alone, response rates were 93% (97.5% CI, 85.4%-100.0%) for patients in the treatment-naive group and 87% (97.5% CI, 75.3%-98.0%) for those in the treatment-experienced group. Three serious adverse events were considered to be treatment related and there were 4 adverse event–related discontinuations. Treatment-emergent grade 3 or 4 alanine aminotransferase elevations were observed in 4 patients, of which 1 had concomitant total bilirubin elevation. Conclusions and Relevance In this open-label uncontrolled study, patients with chronic HCV genotype 1 infection and cirrhosis who received a 12-week oral fixed-dose regimen of daclatasvir, asunaprevir, and beclabuvir, with or without ribavirin, achieved high rates of SVR12

Why is adolescent drinking declining? A systematic review and narrative synthesis

Background: Adolescent drinking has declined across many developed countries from the turn of the century. The aim of this review is to explore existing evidence examining possible reasons for this decline. Methods: We conducted systematic searches across five databases: Medline, PsycINFO, CINAHL, Informit Health and Scopus. Studies were included if association between declining alcohol consumption and potential explanatory factors were measured over time. Narrative synthesis was undertaken due to substantial methodological heterogeneity in these studies. Results: 17 studies met the inclusion criteria. Five studies found moderate evidence for changes in parental practices as a potential cause for the decline. Five studies that examined whether alcohol policy changes influenced the decline found weak evidence of association. Three studies explored whether alcohol use has been substituted by illicit substances but no evidence was found. Two studies examined the effect of a weaker economy; both identified increase in adolescent alcohol use during times of economic crisis. One study indicated that changes in exposure to alcohol advertising were positively associated with the decline and another examined the role of immigration of non-drinking populations but found no evidence of association. One study tested participation in organised sports and party lifestyle as a potential cause but did not use robust analytical methods and therefore did not provide strong evidence of association for the decline. Conclusions: The most robust and consistent evidence was identified for shifts in parental practices. Further research is required using robust analytical methods such as ARIMA modelling techniques and utilising cross-national data