Improved Molecular Diagnostics for Soil-Transmitted Helminths

Current World Health Organization recommendations for the diagnosis of soil-transmitted helminths (STH) rely on antiquated microscopy-based techniques that lack both diagnostic sensitivity and specificity. While sufficient for providing rough estimates of infection frequency and intensity within high prevalence settings, these techniques lack the capacity to effectively estimate infection levels following successful intervention efforts, as worm burdens decline and community prevalences decrease. Furthermore, an expanding body of evidence is suggesting that microscopy-based misdiagnosis of infection is likely a larger concern then previously believed. As such, with an increase in programmatic support for transmission interruption and an escalating belief in the possibility of regional eradication, recognition of the need for improved diagnostics is expanding. Such diagnostics are critically important for accurately measuring intervention successes, and for making determinations about where and when interventions can be discontinued allowing for the re-prioritization of resources. Given the stakes and acknowledging this need, recent years have witnessed the growth of molecular diagnostic development efforts, centering primarily upon the creation of real-time PCR-based assays. However, while a variety of assays have been developed, these assays have all utilized suboptimal DNA targets, typically exploiting ribosomal and/or mitochondrial sequences for parasite detection. By coupling next-generation sequencing with bioinformatics-based approaches to the analysis of raw sequencing read data, the selection of optimal DNA-based molecular targets becomes possible. Software, such as RepeatExplorer can be utilized to identify high copy-number, species-specific, repetitive DNA elements within a pathogen. These repeat sequences can then be utilized to design sensitive and specific real-time PCR assays. Utilizing such an approach, we have designed, developed, and extensively validated a panel of assays facilitating the improved detection of the human infecting STH. These assays are proving useful in a number of settings, gaining widespread traction within the operational research community and helping to shape and define future intervention strategies. Furthermore, our assays continue to highlight the inadequacies of alternative diagnostic methods, illustrating the potential challenges and risks for misdiagnosis associated with the use of both microscopy-based diagnostics, and assays targeting less sensitive, less specific genomic regions

Production de vecteurs viraux efficaces pour la transduction de cellules transformées et de cellules primaires

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal

Analysis of Grasp Requirements for Telerobotic Satellite Servicing

There is an established need to service satellites while on-orbit. Teleoperated robots may conduct this servicing, if the grasps required to perform these tasks are identified and understood. By studying Hubble Space Telescope Servicing Mission 3B, the human grasps used for servicing satellites are identified. Based on the human grasps, a robotic grasp taxonomy is developed. The grasps required for robotic satellite servicing are described in this study in terms of end-effector requirements. Also presented is the relative use of each end-effector. In order to apply the findings here for Servicing Mission 3B to general satellite servicing mission, a task analysis is presented. This displays the end-effector requirements for each type of task performed, which may be applied to similar tasks on future servicing missions

Création d’un matériel pédagogique permettant de développer les compétences en lecture chez les élèves dyslexiques du 2e cycle du primaire en intégrant des concepts de l’éducation musicale

De nos jours, l’apprentissage de la langue écrite est une compétence primordiale à développer pour devenir un individu fonctionnel dans la vie quotidienne. Sachant son importance dans le développement chez les élèves, il faut alors prévoir des interventions pour la réussite de tous. Pour certains, malgré une intervention préventive, l’apprentissage de la lecture demeure tout un défi. Dans la littérature scientifique, certains auteurs mentionnent que l’intégration de la musique en lecture aurait un effet positif sur la performance de celle-ci. L’idée d’intégrer la musique dans des situations d’apprentissage en lecture dans un contexte orthopédagogique prend tout son sens dans cet essai. La recherche-développement s’intéresse à l’apprentissage de la lecture et à l’éducation musicale. Le matériel pédagogique est conçu pour les orthopédagogues qui travaillent avec des élèves dyslexiques du 2e cycle du primaire. Les activités proposées dans le cadre de la création de ce matériel intègre les éléments de l’éducation musicale ainsi que les composantes de la lecture. Ainsi, les trois séquences d’apprentissage créées permettent de développer notamment la compétence du programme de formation de l’école québécoise Lire des textes variés. Chacune des séquences d’apprentissage est divisée en trois périodes. Le matériel pédagogique créé a été évalué par quatre experts qui travaillent dans le domaine de l’éducation. Leurs évaluations diverses ont permis d’améliorer les activités pour une mise à l’essai éventuelle

Understanding the Impact of INDOT Projects on Automotive Industry Cluster Logistics Costs: A Case Study of the Honda Plant

This study focuses on understanding the impact of INDOT projects on the Honda, Greensburg plant’s supply chain. The goal of the study was th

Development of a Novel Real-Time Polymerase Chain Reaction Assay for the Sensitive Detection of Schistosoma Japonicum in Human Stool

Background Elimination and control of Schistosoma japonicum, the most virulent of the schistosomiasiscausing blood flukes, requires the development of sensitive and specific diagnostic tools capable of providing an accurate measurement of the infection prevalence in endemic areas. Typically, detection of S. japonicum has occurred using the Kato-Katz technique, but this methodology, which requires skilled microscopists, has been shown to radically underestimate levels of infection. With the ever-improving capabilities of next-generation sequencing and bioinformatic analysis tools, identification of satellite sequences and other highly repetitive genomic elements for use as real-time PCR diagnostic targets is becoming increasingly common. Assays developed using these targets have the ability to improve the sensitivity and specificity of results for epidemiological studies that can in turn be used to inform mass drug administration and programmatic decision making. Methodology/Principal findings Utilizing Tandem Repeat Analyzer (TAREAN) and RepeatExplorer2, a cluster-based analysis of the S. japonicum genome was performed and a tandemly arranged genomic repeat, which we named SjTR1 (Schistosoma japonicum Tandem Repeat 1), was selected as the target for a real-time PCR diagnostic assay. Based on these analyses, a primer/probe set was designed and the assay was optimized. The resulting real-time PCR test was shown to reliably detect as little as 200 ag of S. japonicum genomic DNA and as little as 1 egg per gram of human stool. Based on these results, the index assay reported in this manuscript is more sensitive than previously published real-time PCR assays for the detection of S. japonicum. Conclusions/Significance The extremely sensitive and specific diagnostic assay described in this manuscript will facilitate the accurate detection of S. japonicum, particularly in regions with low levels of endemicity. This assay will be useful in providing data to inform programmatic decision makers, aiding disease control and elimination efforts

A Superhydrophobic Cone to Facilitate the Xenomonitoring of Filarial Parasites, Malaria, and Trypanosomes Using Mosquito Excreta/Feces

Background: Molecular xenomonitoring (MX), the testing of insect vectors for the presence of human pathogens, has the potential to provide a non-invasive and cost-effective method for monitoring the prevalence of disease within a community. Current MX methods require the capture and processing of large numbers of mosquitoes, particularly in areas of low endemicity, increasing the time, cost and labour required. Screening the excreta/feces (E/F) released from mosquitoes, rather than whole carcasses, improves the throughput by removing the need to discriminate vector species since non-vectors release ingested pathogens in E/F. It also enables larger numbers of mosquitoes to be processed per pool. However, this new screening approach requires a method of efficiently collecting E/F. Methods: We developed a cone with a superhydrophobic surface to allow for the efficient collection of E/F. Using mosquitoes exposed to either Plasmodium falciparum, Brugia malayi or Trypanosoma brucei brucei, we tested the performance of the superhydrophobic cone alongside two other collection methods. Results: All collection methods enabled the detection of DNA from the three parasites. Using the superhydrophobic cone to deposit E/F into a small tube provided the highest number of positive samples (16 out of 18) and facilitated detection of parasite DNA in E/F from individual mosquitoes. Further tests showed that following a simple washing step, the cone can be reused multiple times, further improving its cost-effectiveness. Conclusions: Incorporating the superhydrophobic cone into mosquito traps or holding containers could provide a simple and efficient method for collecting E/F. Where this is not possible, swabbing the container or using the washing method facilitates the detection of the three parasites used in this study