9,279 research outputs found
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Ensuring Access to Safe and Nutritious Food for All Through the Transformation of Food Systems
Omics measures of ageing and disease susceptibility
While genomics has been a major field of study for decades due to relatively inexpensive genotyping arrays, the recent advancement of technology has also allowed the measure and study of various âomicsâ. There are now numerous methods and platforms available that allow high throughput and high dimensional quantification of many types of biological molecules. Traditional genomics and transcriptomics are now joined by proteomics, metabolomics, glycomics, lipidomics and epigenomics.
I was lucky to have access to a unique resource in the Orkney Complex Disease Study (ORCADES), a cohort of individuals from the Orkney Islands that are extremely deeply annotated. Approximately 1000 individuals in ORCADES have genomics, proteomics, lipidomics, glycomics, metabolomics, epigenomics, clinical risk factors and disease phenotypes, as well as body composition measurements from whole body scans. In addition to these cross-sectional omics and health related measures, these individuals also have linked electronic health records (EHR) available, allowing the assessment of the effect of these omics measures on incident disease over a ~10-year follow up period. In this thesis I use this phenotype rich resource to investigate the relationship between multiple types of omics measures and both ageing and health outcomes.
First, I used the ORCADES data to construct measures of biological age (BA). The idea that there is an underlying rate at which the body deteriorates with age that varies between individuals of the same chronological age, this biological age, would be more indicative of health status, functional capacity and risk of age-related diseases than chronological age. Previous models estimating BA (ageing clocks) have predominantly been built using a single type of omics assay and comparison between different omics ageing clocks has been limited. I performed the most exhaustive comparison of different omics ageing clocks yet, with eleven clocks spanning nine different omics assays. I show that different omics clocks overlap in the information they provide about age, that some omics clocks track more generalised ageing while others track specific disease risk factors and that omics ageing clocks are prognostic of incident disease over and above chronological age.
Second, I assessed whether individually or in multivariable models, omics measures are associated with health-related risk factors or prognostic of incident disease over 10 years post-assessment. I show that 2,686 single omics biomarkers are associated with 10 risk factors and 44 subsequent incident diseases. I also show that models built using multiple biomarkers from whole body scans, metabolomics, proteomics and clinical risk factors are prognostic of subsequent diabetes mellitus and that clinical risk factors are prognostic of incident hypertensive disorders, obesity, ischaemic heart disease and Framingham risk score.
Third, I investigated the genetic architecture of a subset of the proteomics measures available in ORCADES, specifically 184 cardiovascular-related proteins. Combining genome-wide association (GWAS) summary statistics from ORCADES and 17 other cohorts from the SCALLOP Consortium, giving a maximum sample size of 26,494 individuals, I performed 184 genome-wide association meta-analyses (GWAMAs) on the levels of these proteins circulating in plasma. I discovered 592 independent significant loci associated with the levels of at least one protein. I found that between 8-37% of these significant loci colocalise with known expression quantitative trait loci (eQTL). I also find evidence of causal associations between 11 plasma protein levels and disease susceptibility using Mendelian randomisation, highlighting potential candidate drug targets
Statistical Learning for Gene Expression Biomarker Detection in Neurodegenerative Diseases
In this work, statistical learning approaches are used to detect biomarkers for neurodegenerative diseases (NDs). NDs are becoming increasingly prevalent as populations age, making understanding of disease and identification of biomarkers progressively important for facilitating early diagnosis and the screening of individuals for clinical trials. Advancements in gene expression profiling has enabled the exploration of disease biomarkers at an unprecedented scale. The work presented here demonstrates the value of gene expression data in understanding the underlying processes and detection of biomarkers of NDs. The value of novel approaches to previously collected -omics data is shown and it is demonstrated that new therapeutic targets can be identified. Additionally, the importance of meta-analysis to improve power of multiple small studies is demonstrated. The value of blood transcriptomics data is shown in applications to researching NDs to understand underlying processes using network analysis and a novel hub detection method. Finally, after demonstrating the value of blood gene expression data for investigating NDs, a combination of feature selection and classification algorithms were used to identify novel accurate biomarker signatures for the diagnosis and prognosis of Parkinsonâs disease (PD) and Alzheimerâs disease (AD). Additionally, the use of feature pools based on previous knowledge of disease and the viability of neural networks in dimensionality reduction and biomarker detection is demonstrated and discussed. In summary, gene expression data is shown to be valuable for the investigation of ND and novel gene biomarker signatures for the diagnosis and prognosis of PD and AD
The Role of Transient Vibration of the Skull on Concussion
Concussion is a traumatic brain injury usually caused by a direct or indirect blow to the head that affects brain function. The maximum mechanical impedance of the brain tissue occurs at 450±50 Hz and may be affected by the skull resonant frequencies. After an impact to the head, vibration resonance of the skull damages the underlying cortex. The skull deforms and vibrates, like a bell for 3 to 5 milliseconds, bruising the cortex. Furthermore, the deceleration forces the frontal and temporal cortex against the skull, eliminating a layer of cerebrospinal fluid. When the skull vibrates, the force spreads directly to the cortex, with no layer of cerebrospinal fluid to reflect the wave or cushion its force. To date, there is few researches investigating the effect of transient vibration of the skull. Therefore, the overall goal of the proposed research is to gain better understanding of the role of transient vibration of the skull on concussion. This goal will be achieved by addressing three research objectives. First, a MRI skull and brain segmentation automatic technique is developed. Due to bonesâ weak magnetic resonance signal, MRI scans struggle with differentiating bone tissue from other structures. One of the most important components for a successful segmentation is high-quality ground truth labels. Therefore, we introduce a deep learning framework for skull segmentation purpose where the ground truth labels are created from CT imaging using the standard tessellation language (STL). Furthermore, the brain region will be important for a future work, thus, we explore a new initialization concept of the convolutional neural network (CNN) by orthogonal moments to improve brain segmentation in MRI. Second, the creation of a novel 2D and 3D Automatic Method to Align the Facial Skeleton is introduced. An important aspect for further impact analysis is the ability to precisely simulate the same point of impact on multiple bone models. To perform this task, the skull must be precisely aligned in all anatomical planes. Therefore, we introduce a 2D/3D technique to align the facial skeleton that was initially developed for automatically calculating the craniofacial symmetry midline. In the 2D version, the entire concept of using cephalometric landmarks and manual image grid alignment to construct the training dataset was introduced. Then, this concept was extended to a 3D version where coronal and transverse planes are aligned using CNN approach. As the alignment in the sagittal plane is still undefined, a new alignment based on these techniques will be created to align the sagittal plane using Frankfort plane as a framework. Finally, the resonant frequencies of multiple skulls are assessed to determine how the skull resonant frequency vibrations propagate into the brain tissue. After applying material properties and mesh to the skull, modal analysis is performed to assess the skull natural frequencies. Finally, theories will be raised regarding the relation between the skull geometry, such as shape and thickness, and vibration with brain tissue injury, which may result in concussive injury
Neural Natural Language Generation: A Survey on Multilinguality, Multimodality, Controllability and Learning
Developing artificial learning systems that can understand and generate natural language has been one of the long-standing goals of artificial intelligence. Recent decades have witnessed an impressive progress on both of these problems, giving rise to a new family of approaches. Especially, the advances in deep learning over the past couple of years have led to neural approaches to natural language generation (NLG). These methods combine generative language learning techniques with neural-networks based frameworks. With a wide range of applications in natural language processing, neural NLG (NNLG) is a new and fast growing field of research. In this state-of-the-art report, we investigate the recent developments and applications of NNLG in its full extent from a multidimensional view, covering critical perspectives such as multimodality, multilinguality, controllability and learning strategies. We summarize the fundamental building blocks of NNLG approaches from these aspects and provide detailed reviews of commonly used preprocessing steps and basic neural architectures. This report also focuses on the seminal applications of these NNLG models such as machine translation, description generation, automatic speech recognition, abstractive summarization, text simplification, question answering and generation, and dialogue generation. Finally, we conclude with a thorough discussion of the described frameworks by pointing out some open research directions.This work has been partially supported by the European Commission ICT COST Action âMulti-task, Multilingual, Multi-modal Language Generationâ (CA18231). AE was supported by BAGEP 2021 Award of the Science Academy. EE was supported in part by TUBA GEBIP 2018 Award. BP is in in part funded by Independent Research Fund Denmark (DFF) grant 9063-00077B. IC has received funding from the European Unionâs Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 838188. EL is partly funded by Generalitat Valenciana and the Spanish Government throught projects PROMETEU/2018/089 and RTI2018-094649-B-I00, respectively. SMI is partly funded by UNIRI project uniri-drustv-18-20. GB is partly supported by the Ministry of Innovation and the National Research, Development and Innovation Office within the framework of the Hungarian Artificial Intelligence National Laboratory Programme. COT is partially funded by the Romanian Ministry of European Investments and Projects through the Competitiveness Operational Program (POC) project âHOLOTRAINâ (grant no. 29/221 ap2/07.04.2020, SMIS code: 129077) and by the German Academic Exchange Service (DAAD) through the project âAWAKEN: content-Aware and netWork-Aware faKE News mitigationâ (grant no. 91809005). ESA is partially funded by the German Academic Exchange Service (DAAD) through the project âDeep-Learning Anomaly Detection for Human and Automated Users Behaviorâ (grant no. 91809358)
Path integral based convolution and pooling for graph neural networks
Graph neural networks (GNNs) extends the functionality of traditional neural networks to graph-structured data. Similar to CNNs, an optimized design of graph convolution and pooling is key to success. Borrowing ideas from physics, we propose a path integral based graph neural networks (PAN) for classification and regression tasks on graphs. Specifically, we consider a convolution operation that involves every path linking the message sender and receiver with learnable weights depending on the path length, which corresponds to the maximal entropy random walk. It generalizes the graph Laplacian to a new transition matrix we call maximal entropy transition (MET) matrix derived from a path integral formalism. Importantly, the diagonal entries of the MET matrix are directly related to the subgraph centrality, thus lead to a natural and adaptive pooling mechanism. PAN provides a versatile framework that can be tailored for different graph data with varying sizes and structures. We can view most existing GNN architectures as special cases of PAN. Experimental results show that PAN achieves state-of-the-art performance on various graph classification/regression tasks, including a new benchmark dataset from statistical mechanics we propose to boost applications of GNN in physical sciences
Conscience and Consciousness: British Theatre and Human Rights.
This research project investigates a paradigm of human rights theatre. Through the lens of performance and theatre-making, this thesis explores how we came to represent, speak about, discuss, and own human rights in Britain. My framework of âhuman rights theatreâ proposes three distinctive features: firstly, such works dramatise real-world issues and highlights the role of the state in endangering its citizens; secondly, ethical ruptures are encountered within and without the drama, and finally, these performances characteristically aspire to produce an activist effect on the collective behaviours of the audience.
This thesis interrogates the strategies theatre-makers use to articulate human rights concerns or to animate human rights intent. The selected case-studies for this investigation are ice&fireâs testimonial project, Actors for Human Rights; Badac Theatre; Jonathan Holmesâ work as director of Jericho House; Cardboard Citizensâ youth participation programme, ACT NOW; and Tony Cealyâs Black Menâs Consortium. Deliberately selecting companies and performance events that have received limited critical attention, my methodology constellates case-studies through original interviews, durational observation of creative working methods and proximate descriptions of practice.
The thesis is interested in the experience of coming to âconsciousnessâ through human rights theatre, an awakening to the impacts of rights infringements and rights claiming. I explore consciousness as a processual, procedural, and durational happening in these performance events. I explore the âĂŠffectâ of activist art and examine the ways in which makers of human rights theatre aim to amplify both affective and effective qualities in their work. My thesis also considers the articulation of activist purpose and the campaigning intent of the selected theatre-makers and explores how their activism is animated in their productions. Through the rich seam of discussion generated by the identification and exploration of the traits of a distinctive human rights theatre, I affirm the generative value of this typological enquiry
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Brain signal recognition using deep learning
This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel UniversityBrain Computer Interface (BCI) has the potential to offer a new generation of applications independent of
muscular activity and controlled by the human brain. Brain imaging technologies are used to transfer the
cognitive tasks into control commands for a BCI system. The electroencephalography (EEG) technology
serves as the best available non-invasive solution for extracting signals from the brain. On the other hand,
speech is the primary means of communication, but for patients suffering from locked-in syndrome, there
is no easy way to communicate. Therefore, an ideal communication system for locked-in patients is a
thought-to-speech BCI system.
This research aims to investigate methods for the recognition of imagined speech from EEG signals
using deep learning techniques. In order to design an optimal imagined speech recognition BCI, variety
of issues have been solved. These include 1) proposing new feature extraction and classification
framework for recognition of imagined speech from EEG signals, 2) grammatical class recognition of
imagined words from EEG signals, 3) discriminating different cognitive tasks associated with speech in
the brain such as overt speech, covert speech, and visual imagery. In this work machine learning, deep
learning methods were used to analyze EEG signals.
For recognition of imagined speech from EEG signals, a new EEG database was collected while the
participants mentally spoke (imagined speech) the presented words. Along with imagined speech, EEG
data was recorded for visual imagery (imagining a scene or an image) and overt speech (verbal speech).
Spectro-temporal and spatio-temporal domain features were investigated for the classification of imagined
words from EEG signals. Further, a deep learning framework using the convolutional network
and attention mechanism was implemented for learning features in the spatial, temporal, and spectral
domains. The method achieved a recognition rate of 76.6% for three binary word pairs. These experiments
show that deep learning algorithms are ideal for imagined speech recognition from EEG signals
due to their ability to interpret features from non-linear and non-stationary signals. Grammatical classes
of imagined words from EEG signals were also recognized using a multi-channel convolution network
framework. This method was extended to a multi-level recognition system for multi-class classification
of imagined words which achieved an accuracy of 52.9% for 10 words, which is much better in
comparison to previous work.
In order to investigate the difference between imagined speech with verbal speech and visual imagery
from EEG signals, we used multivariate pattern analysis (MVPA). MVPA provided the time segments
when the neural oscillation for the different cognitive tasks was linearly separable. Further, frequencies
that result in most discrimination between the different cognitive tasks were also explored. A framework
was proposed to discriminate two cognitive tasks based on the spatio-temporal patterns in EEG signals.
The proposed method used the K-means clustering algorithm to find the best electrode combination and
convolutional-attention network for feature extraction and classification. The proposed method achieved
a high recognition rate of 82.9% and 77.7%.
The results in this research suggest that a communication based BCI system can be designed using
deep learning methods. Further, this work add knowledge to the existing work in the field of communication
based BCI system
Linguistic- and Acoustic-based Automatic Dementia Detection using Deep Learning Methods
Dementia can affect a person's speech and language abilities, even in the early stages. Dementia is incurable, but early detection can enable treatment that can slow down and maintain mental function. Therefore, early diagnosis of dementia is of great importance. However, current dementia detection procedures in clinical practice are expensive, invasive, and sometimes inaccurate. In comparison, computational tools based on the automatic analysis of spoken language have the potential to be applied as a cheap, easy-to-use, and objective clinical assistance tool for dementia detection.
In recent years, several studies have shown promise in this area. However, most studies focus heavily on the machine learning aspects and, as a consequence, often lack sufficient incorporation of clinical knowledge. Many studies also concentrate on clinically less relevant tasks such as the distinction between HC and people with AD which is relatively easy and therefore less interesting both in terms of the machine learning and the clinical application.
The studies in this thesis concentrate on automatically identifying signs of neurodegenerative dementia in the early stages and distinguishing them from other clinical, diagnostic categories related to memory problems: (FMD, MCI, and HC). A key focus, when designing the proposed systems has been to better consider (and incorporate) currently used clinical knowledge and also to bear in mind how these machine-learning based systems could be translated for use in real clinical settings.
Firstly, a state-of-the-art end-to-end system is constructed for extracting linguistic information from automatically transcribed spontaneous speech. The system's architecture is based on hierarchical principles thereby mimicking those used in clinical practice where information at both word-, sentence- and paragraph-level is used when extracting information to be used for diagnosis. Secondly, hand-crafted features are designed that are based on clinical knowledge of the importance of pausing and rhythm. These are successfully joined with features extracted from the end-to-end system. Thirdly, different classification tasks are explored, each set up so as to represent the types of diagnostic decision-making that is relevant in clinical practice. Finally, experiments are conducted to explore how to better deal with the known problem of confounding and overlapping symptoms on speech and language from age and cognitive decline. A multi-task system is constructed that takes age into account while predicting cognitive decline. The studies use the publicly available DementiaBank dataset as well as the IVA dataset, which has been collected by our collaborators at the Royal Hallamshire Hospital, UK. In conclusion, this thesis proposes multiple methods of using speech and language information for dementia detection with state-of-the-art deep learning technologies, confirming the automatic system's potential for dementia detection
Graphical scaffolding for the learning of data wrangling APIs
In order for students across the sciences to avail themselves of modern data streams, they must first know how to wrangle data: how to reshape ill-organised, tabular data into another format, and how to do this programmatically, in languages such as Python and R. Despite the cross-departmental demand and the ubiquity of data wrangling in analytical workflows, the research on how to optimise the instruction of it has been minimal. Although data wrangling as a programming domain presents distinctive challenges - characterised by on-the-fly syntax lookup and code example integration - it also presents opportunities. One such opportunity is how tabular data structures are easily visualised. To leverage the inherent visualisability of data wrangling, this dissertation evaluates three types of graphics that could be employed as scaffolding for novices: subgoal graphics, thumbnail graphics, and parameter graphics. Using a specially built e-learning platform, this dissertation documents a multi-institutional, randomised, and controlled experiment that investigates the pedagogical effects of these. Our results indicate that the graphics are well-received, that subgoal graphics boost the completion rate, and that thumbnail graphics improve navigability within a command menu. We also obtained several non-significant results, and indications that parameter graphics are counter-productive. We will discuss these findings in the context of general scaffolding dilemmas, and how they fit into a wider research programme on data wrangling instruction
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