Development and clinical performance of nucleic acid amplification techniques for the diagnosis of Strongyloides stercoralis

The laboratory diagnosis of Strongyloides stercoralis (S. stercoralis) at the Department of Clinical Parasitology (DCP) by the routine methods of microscopy and Strongyloides culture is not sensitive due to the, usually, low parasite load and intermittent larval excretion of the parasite. Serology (enzyme-linked immunosorbent assay) suffers from a lack of specificity because Strongyloides antibodies are known to cross- react with schistosomal, filarial and other helminthic antibodies in serological tests. Moreover, antibody levels are slow to decline after successful treatment therefore serology cannot be used to monitor point of cure. A missed diagnosis of strongyloidiasis in immunocompromised patients or those about to undergo iatrogenic immune suppression may have severe, even fatal, consequences. The disease is poorly studied because of the lack of sensitive, specific and cost-effective tests. Therefore, the decision was made to evaluate and validate nucleic acid amplification techniques (NAATs) for the diagnosis of S. stercoralis for use in a well- resourced specialist referral parasitology laboratory. A novel loop mediated isothermal amplification (LAMP) assay was also developed for use in resource- limited regions. The study was conducted over two years (2014-2016) and examined 284 residual diagnostic samples. The cohort was drawn from patients attending a central London western travel medicine (WTM) clinic. The NAATs chosen for this study were a published real- time PCR (qPCR) assay (ten Hove et al., 2009) and a novel LAMP assay. The NAATs were compared to the combined reference standard of microscopy, culture and serology for the diagnosis of S. stercoralis in stool samples. The development of the novel LAMP assay for use in resource- limited areas included the investigation of methods for rapid, simple and cost- effective DNA extraction. The qPCR and LAMP assays detect target DNA within areas on either side of the S. stercoralis 18S rRNA genome hypervariable region (Hasegawa et al., 2009). In this study the LAMP and qPCR assays demonstrated a limit of detection of 10-3 and 10-4, respectively for S. stercoralis DNA detection in clinical samples. Specificity was determined for the LAMP and qPCR assays to be 100% and 94.83%, respectively and the cost per test was calculated as £4.80 and £8.21, respectively. In this study, persistence of S. stercoralis DNA in clinical samples was improved when the samples were stored at -20oC. While the LAMP assay has a shorter turnaround time and is less costly than qPCR, the superior efficiency of qPCR detection of S. stercoralis DNA in clinical samples established that the qPCR assay was a more suitable addition to the diagnostic repertoire at a high- throughput WTM clinic. The LAMP assay showed promise for deployment in resource- limited areas and as a point- of- care test but further work is required to optimise the LAMP assay for these purposes

Guidelines for Selecting Professional Development for Early Childhood Teachers

Engaging teachers of young children in effective in-service professional development is a critical component of establishing high quality early childhood education. However, not all professional development offerings are effective in imparting new knowledge, enhancing teacher practice, or improving child outcomes, making it difficult for teachers and directors to select professional development that will benefit their centers. This paper critically reviews the research literature on professional development for early childhood education to identify what features of professional development make a difference for teacher interactions and children’s learning and development. Guidance is provided for selecting professional development opportunities which meet the needs of children and teachers. Recommendations for how to create an ongoing professional development program within an early childhood center by creating a professional learning community are also made. Such an approach supports the center to become a place that values learning and continued education for all professionals

Best practice statement : use of ankle-foot orthoses following stroke

NHS Quality Improvement Scotland (NHSQIS) leads the use of knowledge to promote improvement in the quality of health care for the people of Scotland and performs three key functions. It provides advice and guidance on effective clinical practice, including setting standards; drives and supports implementation of improvements in quality, and assessing the performance of the NHS, reporting and publishing findings

Electron Magnetic Resonance

Contains research objectives.Joint Services Electronics Programs (U. S. Army, U. S. Navy, and U. S. Air Force) under Contract DA 28-043-AMC-02536(E

Electron Magnetic Resonance

Contains research objectives.Joint Services Electronics Programs (U. S. Army, U.S. Navy, and U.S. Air Force) under Contract DA 36-039-AMC-03200(E

Best Practice Statement : Use of Ankle-Foot Orthoses Following Stroke

The development of this Best Practice Statement (BPS) was a collaboration between NHS Quality Improvement Scotland (NHS QIS), National Centre for Prosthetics and Orthotics, University of Strathclyde and a multidisciplinary group of relevant specialists. NHS QIS is a strategic health board which has a lead role in supporting the NHS in Scotland to improve the quality of healthcare. It does this by producing advice and evidence in a number of different formats, including BPS. These statements reflect the commitment of NHS QIS to sharing local excellence at a national level, and the current emphasis on delivering care that is patient-centred, cost-effective and fair. As part of a scoping exercise commissioned by NHS QIS in 2007, allied health professionals (AHPs) across Scotland identified the use of AFOs following stroke in adults as a clinical improvement priority. Orthotic intervention following stroke has been recognised as a treatment option for many years, but there is wide variation in current practice, and a lack of evidence-based research to determine the optimal rehabilitation programme for individuals following stroke. Stroke is the most frequent cause of severe adult disability in Scotland, with approximately 8,500 diagnoses of first-ever stroke each year, and more than 70,000 individuals affected by the condition. A recent Scottish Government strategy document confirms stroke as a national clinical priority for the Scottish NHS. In addition to developing a BPS and sharing this with healthcare professionals across Scotland, the initiative also sought to develop resource material to support the implementation of the BPS and to share the work internationally. In order to inform the development of the BPS a systematic literature review on AFO use following stroke was undertaken, including work of both a qualitative and quantitative nature. The full literature review, together with recommendations for future research, was included in the BPS. As it was felt that many medical professionals and AHPs may be unfamiliar with the principles underpinning orthotic practice, additional educational resources that would improve understanding of the reasons why the recommendations were being made were developed and included in the BPS. In addition to the full BPS, the key recommendations were summarised as a two-page 'quick reference guide' for ease of use in a clinical setting

Numerical recovery of material parameters in Euler-Bernoulli beam models

A fully Sinc-Galerkin method for recovering the spatially varying stiffness parameter in fourth-order time-dependence problems with fixed and cantilever boundary conditions is presented. The forward problems are discretized with a sinc basis in both the spatial and temporal domains. This yields an approximation solution which converges exponentially and is valid on the infinite time interval. When the forward methods are applied to parameter recovery problems, the resulting inverse problems are ill-posed. Tikhonov regularization is applied and the resulting minimization problems are solved via a quasi-Newton/trust region algorithm. The L-curve method is used to determine an appropriate value of the regularization parameter. Numerical results which highlight the method are given for problems with both fixed and cantilever boundary conditions

The trafficking of metal ion transporters of the Zrt‐ and Irt‐like protein family

Metal ion transporters of the Zrt‐ and Irt‐like protein (ZIP, or SLC39A) family transport zinc, iron, manganese and/ or cadmium across cellular membranes and into the cytosol. The 14 human ZIP family proteins are expressed in a wide variety of tissues and function in many different cellular processes. Many of these proteins (including ZIP1, 2, 3, 4, 5, 6/10, 8, 9, 11, 12, 14) are situated, at least some of the time, on the plasma membrane, where they mediate metal ion uptake into cells. Their level on the cell surface can be controlled rapidly via protein trafficking in response to the ions they transport. For example, the cell surface level of many ZIPs (including ZIP1, 3, 4, 8, and 12) is mediated by the available concentration of zinc. Zinc depletion causes a decrease in endocytosis and degradation, resulting in more ZIP on the surface to take up the essential ion. ZIP levels on the cell surface are a balance between endocytosis, recycling and degradation. We review the trafficking mechanisms of human ZIP proteins, highlighting possible targeting motifs and suggesting a model of zinc‐mediated endocytic trafficking. We also provide two possible models for ZIP14 trafficking and degradation

An examination of the spatial distribution of the tissue fragments created during a single explosive attack

Throughout the course of a forensic investigation following an explosive attack, the identification and recovery of tissue fragments is of extreme importance. There are few universally accepted methods to achieve this end. This project aims to explore this issue through the examination of the spatial distribution of the tissue fragments resulting from an explosive event. To address this, a two stage pilot study was conducted: first, a series of controlled explosions on porcine carcases was undertaken. Second, the data produced from these explosions were used to chart the spatial distribution of the tissue debris. In the controlled explosions, 3kg military grade explosive was chosen to create the maximum amount of fragmentation; this level of explosive also prevented the complete disappearance of forensic evidence through evaporation. Additionally, the blast created by military grade explosive is highly powerful and would mean that the maximum possible distance was achieved and would therefore allow the recorded distances and pattern spread to be a guideline for forensic recovery of associated with an explosive amount of an unknown size and quality. A total station was employed to record the location of the resulting forensic evidence, with the collected data analysed using R Studio. The observed patterns suggested that the distribution of remains is fairly consistent in trials under similar environmental conditions. This indicates potential for some general guidelines for forensic evidence collection (for example, the distance from the explosion that a search should cover)