Uma máquina de redução de grafos extensível para a implementação de fluxos de trabalho

Graph Reduction Machines, are a traditional technique for implementing functional programming languages. They allow to run programs by transforming graphs by the successive application of reduction rules. Web service composition enables the creation of new web services from existing ones. BPEL is a workflow-based language for creating web service compositions. It is also the industrial and academic standard for this kind of languages. As it is designed to compose web services, the use of BPEL in a scenario where multiple technologies need to be used is problematic: when operations other than web services need to be performed to implement the business logic of a company, part of the work is done on an ad hoc basis. To allow heterogeneous operations to be part of the same workflow, may help to improve the implementation of business processes in a principled way. This work uses a simple variation of the BPEL language for creating compositions containing not only web service operations but also big data tasks or user-defined operations. We define an extensible graph reduction machine that allows the evaluation of BPEL programs and implement this machine as proof of concept. We present some experimental results.

LCD-OpenPACS: sistema integrado de telerradiologia com auxílio ao diagnóstico de nódulos pulmonares em exames de tomografia computadorizada

Lung cancer is one of the most common types of cancer and has the highest mortality rate. Patient survival is highly correlated with early detection. Computed Tomography technology services the early detection of lung cancer tremendously by offering aminimally invasive medical diagnostic tool. However, the large amount of data per examination makes the interpretation difficult. This leads to omission of nodules by human radiologist. This thesis presents a development of a computer-aided diagnosis system (CADe) tool for the detection of lung nodules in Computed Tomography study. The system, called LCD-OpenPACS (Lung Cancer Detection - OpenPACS) should be integrated into the OpenPACS system and have all the requirements for use in the workflow of health facilities belonging to the SUS (Brazilian health system). The LCD-OpenPACS made use of image processing techniques (Region Growing and Watershed), feature extraction (Histogram of Gradient Oriented), dimensionality reduction (Principal Component Analysis) and classifier (Support Vector Machine). System was tested on 220 cases, totaling 296 pulmonary nodules, with sensitivity of 94.4% and 7.04 false positives per case. The total time for processing was approximately 10 minutes per case. The system has detected pulmonary nodules (solitary, juxtavascular, ground-glass opacity and juxtapleural) between 3 mm and 30 mm.

Fibrous Aerial Robotics: study of spiderweb strategies for the design of architectural envelopes using swarms of drones and inflatable formworks

La tesi approccia in modo transdisciplinare biologia, architettura e robotica, con la finalità di indagare e applicare principi costruttivi attraverso l’interazione tra sciami di droni che depositano materiale fibroso su strutture gonfiabili di supporto. L’attenzione principale è nello sviluppo (attraverso un workflow computazionale che gestisce sciami di agenti costruttori) di una tettonica che integra struttura, spazio e ornamento all’interno dello stesso processo progettuale, il quale si sviluppa coerentemente dall’ideazione fino alla fabbricazione. Sono stati studiati modelli biologici quali le colonie di ragni sociali, i quali costruiscono artefatti di grandi dimensioni relativamente a quelle del singolo individuo grazie ad un’organizzazione coordinata ed emergente e alle proprietà dei sistemi fibrosi. L’auto-organizzazione e la decentralizzazione, insieme alle caratteristiche del sistema materiale, sono stati elementi indispensabili nell’estrapolazione prima e nella codificazione poi di un insieme di regole adatte allo sviluppo del sistema costruttivo. Parallelamente alla simulazione digitale si è andati a sviluppare anche un processo fisico di fabbricazione che, pur tenendo conto dei vincoli economici e tecnici, potesse dimostrarsi una prova di concetto e fattibilità del sistema costruttivo. Sono state investigate le possibilità che un drone offre nel campo della fabbricazione architettonica mediante il rilascio di fili su elementi gonfiabili in pressione. Il processo può risultare vantaggioso in scenari in cui non è possibile allestire infrastrutture costruttive tradizionali (es. gole alpine, foreste). Tendendo conto dei vincoli e delle caratteristiche del sistema di fabbricazione proposto, sono state esplorate potenzialità e criticità del sistema studiato.

Fragilariopsis kerguelensis images from sediment core PS1768-8

Background: Light microscopic analysis of diatom frustules is widely used both in basic and applied research, notably taxonomy, morphometrics, water quality monitoring and paleo-environmental studies. In these applications, usually large numbers of frustules need to be identified and / or measured. Although there is a need for automation in these applications, and image processing and analysis methods supporting these tasks have previously been developed, they did not become widespread in diatom analysis. While methodological reports for a wide variety of methods for image segmentation, diatom identification and feature extraction are available, no single implementation combining a subset of these into a readily applicable workflow accessible to diatomists exists. Results: The newly developed tool SHERPA offers a versatile image processing workflow focused on the identification and measurement of object outlines, handling all steps from image segmentation over object identification to feature extraction, and providing interactive functions for reviewing and revising results. Special attention was given to ease of use, applicability to a broad range of data and problems, and supporting high throughput analyses with minimal manual intervention. Conclusions: Tested with several diatom datasets from different sources and of various compositions, SHERPA proved its ability to successfully analyze large amounts of diatom micrographs depicting a broad range of species. SHERPA is unique in combining the following features: application of multiple segmentation methods and selection of the one giving the best result for each individual object; identification of shapes of interest based on outline matching against a template library; quality scoring and ranking of resulting outlines supporting quick quality checking; extraction of a wide range of outline shape descriptors widely used in diatom studies and elsewhere; minimizing the need for, but enabling manual quality control and corrections. Although primarily developed for analyzing images of diatom valves originating from automated microscopy, SHERPA can also be useful for other object detection, segmentation and outline-based identification problems.

LAPMv2 - software for underwater large-area photo-mosaicking

LAPMv2 is a research software solution specifically developed to allow marine scientists to produce geo-referenced visual maps of the seafloor, known as mosaics, from a set of underwater images and navigation data. LAPMv2 has a graphical user interface that guides the user through the different steps of the mosaicking workflow. LAPMv2 runs on 64-bit Windows, MacOS X and Linux operating systems. There are two versions for each operating system: (1) the WEB-installers (lightweight but require an internet connection during the installation) and (2) the MCR installers (large files but can be installed on computer without internet-connection). The user manual explains how to install and start the program on the different operating systems. Go to http://www.lapm.eu.com for further information about the latest versions of LAPMv2.

Radiotherapy Treatment Assessment using DCE-MRI

Abstract

The goal of modern radiotherapy is to precisely deliver a prescribed radiation dose to delineated target volumes that contain a significant amount of tumor cells while sparing the surrounding healthy tissues/organs. Precise delineation of treatment and avoidance volumes is the key for the precision radiation therapy. In recent years, considerable clinical and research efforts have been devoted to integrate MRI into radiotherapy workflow motivated by the superior soft tissue contrast and functional imaging possibility. Dynamic contrast-enhanced MRI (DCE-MRI) is a noninvasive technique that measures properties of tissue microvasculature. Its sensitivity to radiation-induced vascular pharmacokinetic (PK) changes has been preliminary demonstrated. In spite of its great potential, two major challenges have limited DCE-MRI’s clinical application in radiotherapy assessment: the technical limitations of accurate DCE-MRI imaging implementation and the need of novel DCE-MRI data analysis methods for richer functional heterogeneity information.

This study aims at improving current DCE-MRI techniques and developing new DCE-MRI analysis methods for particular radiotherapy assessment. Thus, the study is naturally divided into two parts. The first part focuses on DCE-MRI temporal resolution as one of the key DCE-MRI technical factors, and some improvements regarding DCE-MRI temporal resolution are proposed; the second part explores the potential value of image heterogeneity analysis and multiple PK model combination for therapeutic response assessment, and several novel DCE-MRI data analysis methods are developed.

I. Improvement of DCE-MRI temporal resolution. First, the feasibility of improving DCE-MRI temporal resolution via image undersampling was studied. Specifically, a novel MR image iterative reconstruction algorithm was studied for DCE-MRI reconstruction. This algorithm was built on the recently developed compress sensing (CS) theory. By utilizing a limited k-space acquisition with shorter imaging time, images can be reconstructed in an iterative fashion under the regularization of a newly proposed total generalized variation (TGV) penalty term. In the retrospective study of brain radiosurgery patient DCE-MRI scans under IRB-approval, the clinically obtained image data was selected as reference data, and the simulated accelerated k-space acquisition was generated via undersampling the reference image full k-space with designed sampling grids. Two undersampling strategies were proposed: 1) a radial multi-ray grid with a special angular distribution was adopted to sample each slice of the full k-space; 2) a Cartesian random sampling grid series with spatiotemporal constraints from adjacent frames was adopted to sample the dynamic k-space series at a slice location. Two sets of PK parameters’ maps were generated from the undersampled data and from the fully-sampled data, respectively. Multiple quantitative measurements and statistical studies were performed to evaluate the accuracy of PK maps generated from the undersampled data in reference to the PK maps generated from the fully-sampled data. Results showed that at a simulated acceleration factor of four, PK maps could be faithfully calculated from the DCE images that were reconstructed using undersampled data, and no statistically significant differences were found between the regional PK mean values from undersampled and fully-sampled data sets. DCE-MRI acceleration using the investigated image reconstruction method has been suggested as feasible and promising.

Second, for high temporal resolution DCE-MRI, a new PK model fitting method was developed to solve PK parameters for better calculation accuracy and efficiency. This method is based on a derivative-based deformation of the commonly used Tofts PK model, which is presented as an integrative expression. This method also includes an advanced Kolmogorov-Zurbenko (KZ) filter to remove the potential noise effect in data and solve the PK parameter as a linear problem in matrix format. In the computer simulation study, PK parameters representing typical intracranial values were selected as references to simulated DCE-MRI data for different temporal resolution and different data noise level. Results showed that at both high temporal resolutions (<1s) and clinically feasible temporal resolution (~5s), this new method was able to calculate PK parameters more accurate than the current calculation methods at clinically relevant noise levels; at high temporal resolutions, the calculation efficiency of this new method was superior to current methods in an order of 102. In a retrospective of clinical brain DCE-MRI scans, the PK maps derived from the proposed method were comparable with the results from current methods. Based on these results, it can be concluded that this new method can be used for accurate and efficient PK model fitting for high temporal resolution DCE-MRI.

II. Development of DCE-MRI analysis methods for therapeutic response assessment. This part aims at methodology developments in two approaches. The first one is to develop model-free analysis method for DCE-MRI functional heterogeneity evaluation. This approach is inspired by the rationale that radiotherapy-induced functional change could be heterogeneous across the treatment area. The first effort was spent on a translational investigation of classic fractal dimension theory for DCE-MRI therapeutic response assessment. In a small-animal anti-angiogenesis drug therapy experiment, the randomly assigned treatment/control groups received multiple fraction treatments with one pre-treatment and multiple post-treatment high spatiotemporal DCE-MRI scans. In the post-treatment scan two weeks after the start, the investigated Rényi dimensions of the classic PK rate constant map demonstrated significant differences between the treatment and the control groups; when Rényi dimensions were adopted for treatment/control group classification, the achieved accuracy was higher than the accuracy from using conventional PK parameter statistics. Following this pilot work, two novel texture analysis methods were proposed. First, a new technique called Gray Level Local Power Matrix (GLLPM) was developed. It intends to solve the lack of temporal information and poor calculation efficiency of the commonly used Gray Level Co-Occurrence Matrix (GLCOM) techniques. In the same small animal experiment, the dynamic curves of Haralick texture features derived from the GLLPM had an overall better performance than the corresponding curves derived from current GLCOM techniques in treatment/control separation and classification. The second developed method is dynamic Fractal Signature Dissimilarity (FSD) analysis. Inspired by the classic fractal dimension theory, this method measures the dynamics of tumor heterogeneity during the contrast agent uptake in a quantitative fashion on DCE images. In the small animal experiment mentioned before, the selected parameters from dynamic FSD analysis showed significant differences between treatment/control groups as early as after 1 treatment fraction; in contrast, metrics from conventional PK analysis showed significant differences only after 3 treatment fractions. When using dynamic FSD parameters, the treatment/control group classification after 1st treatment fraction was improved than using conventional PK statistics. These results suggest the promising application of this novel method for capturing early therapeutic response.

The second approach of developing novel DCE-MRI methods is to combine PK information from multiple PK models. Currently, the classic Tofts model or its alternative version has been widely adopted for DCE-MRI analysis as a gold-standard approach for therapeutic response assessment. Previously, a shutter-speed (SS) model was proposed to incorporate transcytolemmal water exchange effect into contrast agent concentration quantification. In spite of richer biological assumption, its application in therapeutic response assessment is limited. It might be intriguing to combine the information from the SS model and from the classic Tofts model to explore potential new biological information for treatment assessment. The feasibility of this idea was investigated in the same small animal experiment. The SS model was compared against the Tofts model for therapeutic response assessment using PK parameter regional mean value comparison. Based on the modeled transcytolemmal water exchange rate, a biological subvolume was proposed and was automatically identified using histogram analysis. Within the biological subvolume, the PK rate constant derived from the SS model were proved to be superior to the one from Tofts model in treatment/control separation and classification. Furthermore, novel biomarkers were designed to integrate PK rate constants from these two models. When being evaluated in the biological subvolume, this biomarker was able to reflect significant treatment/control difference in both post-treatment evaluation. These results confirm the potential value of SS model as well as its combination with Tofts model for therapeutic response assessment.

In summary, this study addressed two problems of DCE-MRI application in radiotherapy assessment. In the first part, a method of accelerating DCE-MRI acquisition for better temporal resolution was investigated, and a novel PK model fitting algorithm was proposed for high temporal resolution DCE-MRI. In the second part, two model-free texture analysis methods and a multiple-model analysis method were developed for DCE-MRI therapeutic response assessment. The presented works could benefit the future DCE-MRI routine clinical application in radiotherapy assessment.

Identifying the Structure and Fate of Wastewater Derived Organic Micropollutants by High-resolution Mass Spectrometry

Human activities represent a significant burden on the global water cycle, with large and increasing demands placed on limited water resources by manufacturing, energy production and domestic water use. In addition to changing the quantity of available water resources, human activities lead to changes in water quality by introducing a large and often poorly-characterized array of chemical pollutants, which may negatively impact biodiversity in aquatic ecosystems, leading to impairment of valuable ecosystem functions and services. Domestic and industrial wastewaters represent a significant source of pollution to the aquatic environment due to inadequate or incomplete removal of chemicals introduced into waters by human activities. Currently, incomplete chemical characterization of treated wastewaters limits comprehensive risk assessment of this ubiquitous impact to water. In particular, a significant fraction of the organic chemical composition of treated industrial and domestic wastewaters remains uncharacterized at the molecular level. Efforts aimed at reducing the impacts of water pollution on aquatic ecosystems critically require knowledge of the composition of wastewaters to develop interventions capable of protecting our precious natural water resources.

The goal of this dissertation was to develop a robust, extensible and high-throughput framework for the comprehensive characterization of organic micropollutants in wastewaters by high-resolution accurate-mass mass spectrometry. High-resolution mass spectrometry provides the most powerful analytical technique available for assessing the occurrence and fate of organic pollutants in the water cycle. However, significant limitations in data processing, analysis and interpretation have limited this technique in achieving comprehensive characterization of organic pollutants occurring in natural and built environments. My work aimed to address these challenges by development of automated workflows for the structural characterization of organic pollutants in wastewater and wastewater impacted environments by high-resolution mass spectrometry, and to apply these methods in combination with novel data handling routines to conduct detailed fate studies of wastewater-derived organic micropollutants in the aquatic environment.

In Chapter 2, chemoinformatic tools were implemented along with novel non-targeted mass spectrometric analytical methods to characterize, map, and explore an environmentally-relevant “chemical space” in municipal wastewater. This was accomplished by characterizing the molecular composition of known wastewater-derived organic pollutants and substances that are prioritized as potential wastewater contaminants, using these databases to evaluate the pollutant-likeness of structures postulated for unknown organic compounds that I detected in wastewater extracts using high-resolution mass spectrometry approaches. Results showed that application of multiple computational mass spectrometric tools to structural elucidation of unknown organic pollutants arising in wastewaters improved the efficiency and veracity of screening approaches based on high-resolution mass spectrometry. Furthermore, structural similarity searching was essential for prioritizing substances sharing structural features with known organic pollutants or industrial and consumer chemicals that could enter the environment through use or disposal.

I then applied this comprehensive methodological and computational non-targeted analysis workflow to micropollutant fate analysis in domestic wastewaters (Chapter 3), surface waters impacted by water reuse activities (Chapter 4) and effluents of wastewater treatment facilities receiving wastewater from oil and gas extraction activities (Chapter 5). In Chapter 3, I showed that application of chemometric tools aided in the prioritization of non-targeted compounds arising at various stages of conventional wastewater treatment by partitioning high dimensional data into rational chemical categories based on knowledge of organic chemical fate processes, resulting in the classification of organic micropollutants based on their occurrence and/or removal during treatment. Similarly, in Chapter 4, high-resolution sampling and broad-spectrum targeted and non-targeted chemical analysis were applied to assess the occurrence and fate of organic micropollutants in a water reuse application, wherein reclaimed wastewater was applied for irrigation of turf grass. Results showed that organic micropollutant composition of surface waters receiving runoff from wastewater irrigated areas appeared to be minimally impacted by wastewater-derived organic micropollutants. Finally, Chapter 5 presents results of the comprehensive organic chemical composition of oil and gas wastewaters treated for surface water discharge. Concurrent analysis of effluent samples by complementary, broad-spectrum analytical techniques, revealed that low-levels of hydrophobic organic contaminants, but elevated concentrations of polymeric surfactants, which may effect the fate and analysis of contaminants of concern in oil and gas wastewaters.

Taken together, my work represents significant progress in the characterization of polar organic chemical pollutants associated with wastewater-impacted environments by high-resolution mass spectrometry. Application of these comprehensive methods to examine micropollutant fate processes in wastewater treatment systems, water reuse environments, and water applications in oil/gas exploration yielded new insights into the factors that influence transport, transformation, and persistence of organic micropollutants in these systems across an unprecedented breadth of chemical space.

Data-Driven Motion Detection and Characterization in PET Brain Scans Using List Mode

Head motion during a Positron Emission Tomography (PET) brain scan can considerably degrade image quality. External motion-tracking devices have proven successful in minimizing this effect, but the associated time, maintenance, and workflow changes inhibit their widespread clinical use. List-mode PET acquisition allows for the retroactive analysis of coincidence events on any time scale throughout a scan, and therefore potentially offers a data-driven motion detection and characterization technique. An algorithm was developed to parse list-mode data, divide the full acquisition into short scan intervals, and calculate the line-of-response (LOR) midpoint average for each interval. These LOR midpoint averages, known as “radioactivity centroids,” were presumed to represent the center of the radioactivity distribution in the scanner, and it was thought that changes in this metric over time would correspond to intra-scan motion.

Several scans were taken of the 3D Hoffman brain phantom on a GE Discovery IQ PET/CT scanner to test the ability of the radioactivity to indicate intra-scan motion. Each scan incrementally surveyed motion in a different degree of freedom (2 translational and 2 rotational). The radioactivity centroids calculated from these scans correlated linearly to phantom positions/orientations. Centroid measurements over 1-second intervals performed on scans with ~1mCi of activity in the center of the field of view had standard deviations of 0.026 cm in the x- and y-dimensions and 0.020 cm in the z-dimension, which demonstrates high precision and repeatability in this metric. Radioactivity centroids are thus shown to successfully represent discrete motions on the submillimeter scale. It is also shown that while the radioactivity centroid can precisely indicate the amount of motion during an acquisition, it fails to distinguish what type of motion occurred.

A stereo-image analysis JAVA software with links to executable and source code

Scientists planning to use underwater stereoscopic image technologies are often faced with numerous problems during the methodological implementations: commercial equipment is too expensive; the setup or calibration is too complex; or the imaging processing (i.e. measuring objects in the stereo-images) is too complicated to be performed without a time-consuming phase of training and evaluation. The present paper addresses some of these problems and describes a workflow for stereoscopic measurements for marine biologists. It also provides instructions on how to assemble an underwater stereo-photographic system with two digital consumer cameras and gives step-by-step guidelines for setting up the hardware. The second part details a software procedure to correct stereo-image pairs for lens distortions, which is especially important when using cameras with non-calibrated optical units. The final part presents a guide to the process of measuring the lengths (or distances) of objects in stereoscopic image pairs. To reveal the applicability and the restrictions of the described systems and to test the effects of different types of camera (a compact camera and an SLR type), experiments were performed to determine the precision and accuracy of two generic stereo-imaging units: a diver-operated system based on two Olympus Mju 1030SW compact cameras and a cable-connected observatory system based on two Canon 1100D SLR cameras. In the simplest setup without any correction for lens distortion, the low-budget Olympus Mju 1030SW system achieved mean accuracy errors (percentage deviation of a measurement from the object's real size) between 10.2 and -7.6% (overall mean value: -0.6%), depending on the size, orientation and distance of the measured object from the camera. With the single lens reflex (SLR) system, very similar values between 10.1% and -3.4% (overall mean value: -1.2%) were observed. Correction of the lens distortion significantly improved the mean accuracy errors of either system. Even more, system precision (spread of the accuracy) improved significantly in both systems. Neither the use of a wide-angle converter nor multiple reassembly of the system had a significant negative effect on the results. The study shows that underwater stereophotography, independent of the system, has a high potential for robust and non-destructive in situ sampling and can be used without prior specialist training.

ThreeDimensional Epigraphic Recording at Stobi (Former Yugoslav Republic of Macedonia): Creating a Virtual Lapidarium

There is an increased need for 3D recording of archaeological sites and digital preservation of their artifacts. Digital photogrammetry with prosumer DSLR cameras is a suitable tool for recording epigraphy in particular, as it allows for the recording of inscribed surfaces with very high accuracy, often better than 2 mm and with only a short time spent in the field. When photogrammetry is fused with other computational photography techniques like panoramic tours and Reflectance Transformation Imaging, a workflow exists to rival traditional LiDAR­based methods. The difficulty however, arises in the presentation of 3D data. It requires an enormous amount of storage and end­user sophistication. The proposed solution is to use game­engine technology and high definition virtual tours to provide not only scholars, but also the general public with an uncomplicated interface to interact with the detailed 3D epigraphic data. The site of Stobi, located near Gradsko, in the Former Yugoslav Republic of Macedonia (FYROM) was used as a case study to demonstrate the effectiveness of RTI, photogrammetry and virtual tour imaging working in combination. A selection of nine sets of inscriptions from the archaeological site were chosen to demonstrate the range of application for the techniques. The chosen marble, sandstone and breccia inscriptions are representative of the varying levels of deterioration and degradation of the epigraphy at Stobi, in which both their rates of decay and resulting legibility is varied. This selection includes those which are treated and untreated stones as well as those in situ and those in storage. The selection consists of both Latin and Greek inscriptions with content ranging from temple dedication inscriptions to statue dedications. This combination of 3D modeling techniques presents a cost and time efficient solution to both increase the legibility of severely damaged stones and to digitally preserve the current state of the inscriptions.

Extending Science Gateway Frameworks to Support Big Data Applications in the Cloud

Cloud computing offers massive scalability and elasticity required by many scien-tific and commercial applications. Combining the computational and data handling capabilities of clouds with parallel processing also has the potential to tackle Big Data problems efficiently. Science gateway frameworks and workflow systems enable application developers to implement complex applications and make these available for end-users via simple graphical user interfaces. The integration of such frameworks with Big Data processing tools on the cloud opens new oppor-tunities for application developers. This paper investigates how workflow sys-tems and science gateways can be extended with Big Data processing capabilities. A generic approach based on infrastructure aware workflows is suggested and a proof of concept is implemented based on the WS-PGRADE/gUSE science gateway framework and its integration with the Hadoop parallel data processing solution based on the MapReduce paradigm in the cloud. The provided analysis demonstrates that the methods described to integrate Big Data processing with workflows and science gateways work well in different cloud infrastructures and application scenarios, and can be used to create massively parallel applications for scientific analysis of Big Data.

Building a Rockfall Database Using Remote Sensing: Techniques for Hazard Management in Canadian Rail Corridors

The section of CN railway between Vancouver and Kamloops runs along the base of many hazardous slopes, including the White Canyon, which is located just outside the town of Lytton, BC. The slope has a history of frequent rockfall activity, which presents a hazard to the railway below. Rockfall inventories can be used to understand the frequency-magnitude relationship of events on hazardous slopes, however it can be difficult to consistently and accurately identify rockfall source zones and volumes on large slopes with frequent activity, leaving many inventories incomplete. We have studied this slope as a part of the Canadian Railway Ground Hazard Research Program and have collected remote sensing data, including terrestrial laser scanning (TLS), photographs, and photogrammetry data since 2012, and used change detection to identify rockfalls on the slope. The objective of this thesis is to use a subset of this data to understand how rockfalls identified from TLS data could be used to understand the frequency-magnitude relationship of rockfalls on the slope. This includes incorporating both new and existing methods to develop a semi-automated workflow to extract rockfall events from the TLS data. We show that these methods can be used to identify events as small as 0.01 m3 and that the duration between scans can have an effect on the frequency-magnitude relationship of the rockfalls. We also show that by incorporating photogrammetry data into our analysis, we can create a 3D geological model of the slope and use this to classify rockfalls by lithology, to further understand the rockfall failure patterns. When relating the rockfall activity to triggering factors, we found that the amount of precipitation occurring over the winter has an effect on the overall rockfall frequency for the remainder of the year. These results can provide the railways with a more complete inventory of events compared to records created through track inspection, or rockfall monitoring systems that are installed on the slope. In addition, we can use the database to understand the spatial and temporal distribution of events. The results can also be used as an input to rockfall modelling programs.

Multi-Scale Visualization and Interpretation of Geological Relationships

Visualization and interpretation of geological observations into a cohesive geological model are essential to Earth sciences and related fields. Various emerging technologies offer approaches to multi-scale visualization of heterogeneous data, providing new opportunities that facilitate model development and interpretation processes. These include increased accessibility to 3D scanning technology, global connectivity, and Web-based interactive platforms. The geological sciences and geological engineering disciplines are adopting these technologies as volumes of data and physical samples greatly increase. However, a standardized and universally agreed upon workflow and approach have yet to properly be developed. In this thesis, the 3D scanning workflow is presented as a foundation for a virtual geological database. This database provides augmented levels of tangibility to students and researchers who have little to no access to locations that are remote or inaccessible. A Web-GIS platform was utilized jointly with customized widgets developed throughout the course of this research to aid in visualizing hand-sized/meso-scale geological samples within a geologic and geospatial context. This context is provided as a macro-scale GIS interface, where geophysical and geodetic images and data are visualized. Specifically, an interactive interface is developed that allows for simultaneous visualization to improve the understanding of geological trends and relationships. These developed tools will allow for rapid data access and global sharing, and will facilitate comprehension of geological models using multi-scale heterogeneous observations.

Inter-Laboratory Evaluation of a Next-Generation Sequencing Panel for Acute Myeloid Leukemia

INTRODUCTION: Acute myeloid leukemia (AML) is a heterogeneous clonal disorder often associated with dismal overall survival. The clinical diversity of AML is reflected in the range of recurrent somatic mutations in several genes, many of which have a prognostic and therapeutic value. Targeted next-generation sequencing (NGS) of these genes has the potential for translation into clinical practice. In order to assess this potential, an inter-laboratory evaluation of a commercially available AML gene panel across three diagnostic centres in the UK and Ireland was performed.

METHODS: DNA from six AML patient samples was distributed to each centre and processed using a standardised workflow, including a common sequencing platform, sequencing chips and bioinformatics pipeline. A duplicate sample in each centre was run to assess inter- and intra-laboratory performance.

RESULTS: An average sample read depth of 2725X (range 629-5600) was achieved using six samples per chip, with some variability observed in the depth of coverage generated for individual samples and between centres. A total of 16 somatic mutations were detected in the six AML samples, with a mean of 2.7 mutations per sample (range 1-4) representing nine genes on the panel. 15/16 mutations were identified by all three centres. Allelic frequencies of the mutations ranged from 5.6 to 53.3 % (median 44.4 %), with a high level of concordance of these frequencies between centres, for mutations detected.

CONCLUSION: In this inter-laboratory comparison, a high concordance, reproducibility and robustness was demonstrated using a commercially available NGS AML gene panel and platform.

Variation in pre-PCR processing of FFPE samples leads to discrepancies in BRAF and EGFR mutation detection: a diagnostic RING trial.

AIMS: Mutation detection accuracy has been described extensively; however, it is surprising that pre-PCR processing of formalin-fixed paraffin-embedded (FFPE) samples has not been systematically assessed in clinical context. We designed a RING trial to (i) investigate pre-PCR variability, (ii) correlate pre-PCR variation with EGFR/BRAF mutation testing accuracy and (iii) investigate causes for observed variation. METHODS: 13 molecular pathology laboratories were recruited. 104 blinded FFPE curls including engineered FFPE curls, cell-negative FFPE curls and control FFPE tissue samples were distributed to participants for pre-PCR processing and mutation detection. Follow-up analysis was performed to assess sample purity, DNA integrity and DNA quantitation. RESULTS: Rate of mutation detection failure was 11.9%. Of these failures, 80% were attributed to pre-PCR error. Significant differences in DNA yields across all samples were seen using analysis of variance (p