Diagnosis of speech errors in children with autism using ultrasound

Background Fine motor control is frequently impaired in children with autism, however, speech motor control has been found to be unimpaired in some studies using perceptual methods. This is despite the need for intricate movement of the tongue required for accurate speech. However, a small number of studies found residual and non-developmental speech errors are significantly higher in a sample of children with autism (33-40%) than the normal adult population (1-2%; Shriberg et al., 2001; Cleland et al., 2010). Conflicting evidence may be due to unreliable perceptual analysis that relies on auditory skills of the assessor. The cause of these speech errors is still in debate. Aim of the study Our research will investigate speech errors in autism using Ultrasound Tongue Imaging (UTI). It will be used to identify any inaccurate or uncoordinated movements of the tongue which could indicate a motor impairment. We aim to determine whether errors in fine motor control are echoed in errors of speech. Using UTI eliminates the higher likelihood of variation and inaccuracy of perceptual assessments. Additionally, we will compare UTI and perceptual assessments to determine whether there are speech errors missed in the clinic through the use of perceptual assessments only. Methods We will compare UTI data with standardized speech assessments. UTI is used in the imaging of speech as it allows investigation of tongue movement. By placing a standard medical ultrasound probe under the chin, most of the surface of the tongue in a midsagittal view is imaged. UTI has been used in the field for decades however until recently it was hard to gain useful data from. Now ultrasound is portable, provides fast frame rates and can synchronize ultrasound images with audio. This allows analysis of tongue movement that can be compared across participants. Fine motor control will be assessed using standardized assessment and specific fine motor measurements. All assessments will analyse the coordination and accuracy of movements of fingers and speech muscles. Conclusions/importance of work It is important to investigate the relationship between speech motor control and fine motor control as it can ultimately change the treatment provided by speech and language therapists (SLTs). If speech errors in autism are a result of a motor control difficulty then traditional speech therapy is less likely to be successful. Therapy needs to specifically target speech motor planning. If perceptual assessments are not sensitive enough to identify speech errors in autism, UTI may be an effective instrument to improve diagnostic accuracy to inform practice

Action of earthworms on flint burial – a return to Darwin’s estate

For thirty years, from the early 1840s, Charles Darwin documented the disappearance of flints in the grounds of Down House in Kent, at a location originally known as the “Stony Field”. This site (Great Pucklands Meadow - GPM) was visited in 2007 and an experiment set up in this ungrazed grassland. Locally-sourced flints (either large - 12 cm, or small – 5 cm dia.) were deposited at two densities within sixteen 1 m2 plots in a randomised factorial design. The area selected was distant from public access routes and remained unmown throughout the duration here reported. Fixed point photographs were taken at the outset to enable later photogrammetric analysis. After 6 years, the site was re-examined. The flints had generally been incorporated into the soil. Photographs were re-taken, proportion of buried flints recorded and measurements made of burial depth from a quarter of each plot. Results showed that large flints were more deeply incorporated than smaller (p=0.025), but more of the latter were below the soil surface. A controlled laboratory experiment was also conducted using Aporrectodea longa (the dominant earthworm species in GPM) to assess effects of casting in the absence of other biota. Results suggested that this species has a major influence on flint burial through surface casting. Combined with a long term, but small scale collection of A. longa casts from an area close to GPM, all results were consistent with those provided by Darwin and showed that rate of flint burial was within the range 0.21-0.96 cm y-1

Exploring the Usability of Game-Based Virtual Reality for Development of Procedural Skills in Undergraduate Nursing Students

Providing safe, high quality patient care requires that undergraduate nursing students learn and apply extensive content knowledge as they also begin to develop clinical judgment. Nursing students must learn several procedural skills and be ready to remember and competently perform these skills when the need arises during patient care. Some procedures require strict adherence to aseptic technique in order to protect patients from hospital-acquired infections. Consequently, nurse educators are challenged to find innovative and interactive ways to help students develop and remember these important fundamental skills while ensuring patient safety. This study used a mixed methods design to explore the usability of, and user-reaction to, a game-based virtual reality (VR) system. The unique system combines headgear and haptics to place the nursing student in a patient’s room in order to practice inserting a urinary catheter virtually. The study also compared control and experimental participants’ time-on-task, number of procedures completed in one hour, and ability to demonstrate aseptic technique during urinary catheter insertion two weeks post-practice session. All study participants were given one hour to practice catheter insertion, either on a task trainer or virtually. User reactions to the VR game were observed during gameplay and collected via survey immediately after each individual VR game practice session. Subjects rated the system solidly in the Acceptable range using the System Usability Survey (Brooke, 1996) and between Good and Excellent when including a comparative adjective rating scale (Bangor, Kortum, & Miller, 2009). Inclusion of minimal game elements (points and a timer) motivated participants to continue to practice in order to improve their scores and procedure completion time, as well as engage in competition against their peers. Subjects in the experimental group spent more time practicing and completed more procedures than subjects in the control group and rated the experience as highly engaging and enjoyable. The pass rate at two week follow-up catheter insertion demonstration was 60% for both groups. Results of this study suggest that combining VR technology with game-based learning provides an innovative and useful way for students to practice procedural skills prior to performing the procedure on patients. The next iteration of the system will include an emphasis on providing clearer feedback to promote more accurate practice and should then be tested on larger numbers of students at multiple sites

An improved method for surface immobilisation of RNA: application to small Non-Coding RNA - mRNA pairing

Characterisation of RNA and its intermolecular interactions is increasing in importance as the inventory of known RNA functions continues to expand. RNA-RNA interactions are central to post-transcriptional gene regulation mechanisms in bacteria, and the interactions of bacterial small non-coding RNAs (sRNAs) with their mRNA targets are the subject of much current research. The technology of surface plasmon resonance (SPR) is an attractive approach to studying these interactions since it is highly sensitive, and allows interaction measurements to be recorded in real-time. Whilst a number of approaches exist to label RNAs for surface-immobilisation, the method documented here is simple, quick, efficient, and utilises the high-affinity streptavidin-biotin interaction. Specifically, we ligate a biotinylated nucleotide to the 3' end of RNA using T4 RNA ligase. Although this is a previously recognised approach, we have optimised the method by our discovery that the incorporation of four or more adenine nucleotides at the 3' end of the RNA (a poly-A-tail) is required in order to achieve high ligation efficiencies. We use this method within the context of investigating small non-coding RNA (sRNA)-mRNA interactions through the application of surface technologies, including quantitative SPR assays. We first focus on validating the method using the recently characterised Escherichia coli sRNA-mRNA pair, MicA-ompA, specifically demonstrating that the addition of the poly-A-tail to either RNA does not affect its subsequent binding interactions with partner molecules. We then apply this method to investigate the novel interactions of a Vibrio cholerae Qrr sRNA with partner mRNAs, hapR and vca0939; RNA-RNA pairings that are important in mediating pathogenic virulence. The calculated binding parameters allow insights to be drawn regarding sRNA-mRNA interaction mechanisms

High-density functional-RNA arrays as a versatile platform for studying RNA-based interactions

We are just beginning to unravel the myriad of interactions in which non-coding RNAs participate. The intricate RNA interactome is the foundation of many biological processes, including bacterial virulence and human disease, and represents unexploited resources for the development of potential therapeutic interventions. However, identifying specific associations of a given RNA from the multitude of possible binding partners within the cell requires robust high-throughput systems for their rapid screening. Here, we present the first demonstration of functional-RNA arrays as a novel platform technology designed for the study of such interactions using immobilized, active RNAs. We have generated high-density RNA arrays by an innovative method involving surface-capture of in vitro transcribed RNAs. This approach has significant advantages over existing technologies, particularly in its versatility in regards to binding partner character. Indeed, proof-of-principle application of RNA arrays to both RNA-small molecule and RNA-RNA pairings is demonstrated, highlighting their potential as a platform technology for mapping RNA-based networks and for pharmaceutical screening. Furthermore, the simplicity of the method supports greater user-accessibility over currently available technologies. We anticipate that functional-RNA arrays will find broad utility in the expanding field of RNA characterization

An Investigation into the Potential of Targeting Escherichia coli rne mRNA with Locked Nucleic Acid (LNA) Gapmers as an Antibacterial Strategy

The increase in antibacterial resistance is a serious challenge for both the health and defence sectors and there is a need for both novel antibacterial targets and antibacterial strategies. RNA degradation and ribonucleases, such as the essential endoribonuclease RNase E, encoded by the rne gene, are emerging as potential antibacterial targets while antisense oligonucleotides may provide alternative antibacterial strategies. As rne mRNA has not been previously targeted using an antisense approach, we decided to explore using antisense oligonucleotides to target the translation initiation region of the Escherichia coli rne mRNA. Antisense oligonucleotides were rationally designed and were synthesised as locked nucleic acid (LNA) gapmers to enable inhibition of rne mRNA translation through two mechanisms. Either LNA gapmer binding could sterically block translation and/or LNA gapmer binding could facilitate RNase H-mediated cleavage of the rne mRNA. This may prove to be an advantage over the majority of previous antibacterial antisense oligonucleotide approaches which used oligonucleotide chemistries that restrict the mode-of-action of the antisense oligonucleotide to steric blocking of translation. Using an electrophoretic mobility shift assay, we demonstrate that the LNA gapmers bind to the translation initiation region of E. coli rne mRNA. We then use a cell-free transcription translation reporter assay to show that this binding is capable of inhibiting translation. Finally, in an in vitro RNase H cleavage assay, the LNA gapmers facilitate RNase H-mediated mRNA cleavage. Although the challenges of antisense oligonucleotide delivery remain to be addressed, overall, this work lays the foundations for the development of a novel antibacterial strategy targeting rne mRNA with antisense oligonucleotides

Should patients with abnormal liver function tests in primary care be tested for chronic viral hepatitis: cost minimisation analysis based on a comprehensively tested cohort

Background Liver function tests (LFTs) are ordered in large numbers in primary care, and the Birmingham and Lambeth Liver Evaluation Testing Strategies (BALLETS) study was set up to assess their usefulness in patients with no pre-existing or self-evident liver disease. All patients were tested for chronic viral hepatitis thereby providing an opportunity to compare various strategies for detection of this serious treatable disease. Methods This study uses data from the BALLETS cohort to compare various testing strategies for viral hepatitis in patients who had received an abnormal LFT result. The aim was to inform a strategy for identification of patients with chronic viral hepatitis. We used a cost-minimisation analysis to define a base case and then calculated the incremental cost per case detected to inform a strategy that could guide testing for chronic viral hepatitis. Results Of the 1,236 study patients with an abnormal LFT, 13 had chronic viral hepatitis (nine hepatitis B and four hepatitis C). The strategy advocated by the current guidelines (repeating the LFT with a view to testing for specific disease if it remained abnormal) was less efficient (more expensive per case detected) than a simple policy of testing all patients for viral hepatitis without repeating LFTs. A more selective strategy of viral testing all patients for viral hepatitis if they were born in countries where viral hepatitis was prevalent provided high efficiency with little loss of sensitivity. A notably high alanine aminotransferase (ALT) level (greater than twice the upper limit of normal) on the initial ALT test had high predictive value, but was insensitive, missing half the cases of viral infection. Conclusions Based on this analysis and on widely accepted clinical principles, a "fast and frugal" heuristic was produced to guide general practitioners with respect to diagnosing cases of viral hepatitis in asymptomatic patients with abnormal LFTs. It recommends testing all patients where a clear clinical indication of infection is present (e.g. evidence of intravenous drug use), followed by testing all patients who originated from countries where viral hepatitis is prevalent, and finally testing those who have a notably raised ALT level (more than twice the upper limit of normal). Patients not picked up by this efficient algorithm had a risk of chronic viral hepatitis that is lower than the general population

How do we enhance linked administrative data based chronic disease surveillance in Canada? Results of an environmental scan.

Introduction The Canadian Chronic Disease Surveillance System (CCDSS) is a collaboration of provincial and territorial surveillance systems which generates estimates of chronic diseases using linked population-level administrative health databases and standard case definitions. We conducted an environmental scan of administrative data validation studies and identified opportunities for CCDSS case definition enhancement. Objectives and Approach The purpose of this project is to develop a methodology for and conduct an environmental scan, identifying opportunities for enhancing the CCDSS. This multifaceted approach consists of the following elements: 1) key informant interviews and stakeholder consultations to identify new and existing priority conditions for updating/validating within the CCDSS, and new areas of conceptual and methodological relevance for administrative data disease surveillance, 2) a systematic literature review of PubMed, Ovid and Embase from 2013-2017 using MeSH terms and a librarian peer-reviewed search strategy, and 3) a review of the grey literature. Results Key stakeholders identified the following priorities for validation work and/or case definition enhancement: diabetes, mood and anxiety disorders, schizophrenia, obesity, hypertension, chronic obstructive pulmonary disease, osteoarthritis, stroke, early-onset dementia, rheumatoid arthritis and gout. Scientific and grey literature reviews of validation work for these conditions examined the following concepts/methods: 1) evaluating validity of disease-specific case definitions over time, and in different ages, sub-populations and settings, 2) defining incidence versus prevalence using linked administrative data, 3) determining opportunities and constraints of using linked administrative data to conduct surveillance on diseases that are chronic versus episodic in nature and defining active versus lifetime prevalence, and 4) assessing the feasibility of using new sources of data for linkage to enhance case definition validity. Conclusion/Implications Utilization of linked administrative databases for chronic disease surveillance has expanded across many jurisdictions since the inception of the CCDSS. As disease estimates generated in this manner are increasingly being relied upon by policy makers working to enhance public health, the methodological opportunities and constraints identified here require consideration