{3D} Morphable Face Models -- Past, Present and Future

In this paper, we provide a detailed survey of 3D Morphable Face Models over the 20 years since they were first proposed. The challenges in building and applying these models, namely capture, modeling, image formation, and image analysis, are still active research topics, and we review the state-of-the-art in each of these areas. We also look ahead, identifying unsolved challenges, proposing directions for future research and highlighting the broad range of current and future applications

The potential impact of genotype-driven precision medicine for children with epilepsy

Introduction: The development and application of next generation sequencing (NGS) technology has led to an exponential rise in the number of genes and genetic variants associated with epilepsy. The detection of highly penetrant and damaging variants in some patients can be sufficient to provide an adequate explanation for the entire disease process. Particularly high yields from such diagnostic genetic testing are observed in cohorts of children who present with early onset seizures. Obtaining a genetic diagnosis can be helpful to families in terms of informing further reproductive decisions, providing answers, and preventing further costly investigations. Evidence is emerging that certain anti-epileptic therapies may be more effective than others in specific genetic epilepsies. Aim: The aim of this thesis is to explore the potential for genetically-guided therapy for children with epilepsy. This will be primarily achieved through describing the epidemiology of the genetic epilepsies of childhood, and through researching the evidence-base for gene-specific therapy. Methods: This is a mixed methods study. In chapter 5 The epidemiology of early childhood genetic epilepsy is described using a prospective whole Scotland population based national cohort. This includes all children presenting under three years of age presenting with new onset epilepsy over a defined time period (May 2014 to May 2017, n =315). These children were tested on a panel of 104 epilepsy-associated genes. In chapter 6 the potential for Whole Genome Sequencing (WGS) to identify further genetic diagnoses in deeply-phenotyped families is then explored in a separate cohort of children presenting in the West of Scotland with severe or drug-resistant epilepsy (n = 79). In chapter 4, a systematic review approach is used to identify any epilepsy-associated genes for which evidence exists to support a specific therapeutic approach. The results from this review considered in both cohorts. Chapter 7 describes a new genetic epilepsy due to SMC1A truncation and explores the potential for specific therapy in this condition. Chapter 8 evaluates whether sub-analysis of genetic data within a randomised controlled trial can be harnessed to identify patients most likely to respond to therapy. Key results: Epilepsy affects 1 per 383 children before their third birthday. In 22% of these children a single-gene cause can be identified. For 80% per cent of single-gene diagnoses in this group of patients there is some evidence to support a specific therapeutic approach. Evidence is variable in quality and nature. Between 1 in 2,000 and 1 in 2,300 of all children born are likely to have a genetically determined epilepsy for which there is currently available some evidence for a specific treatment choice. The majority of currently achievable genetic diagnoses are concentrated in a small number of genes, with genetic diagnoses beyond the 20 most common being extremely individually rare. Evidence to support specific therapeutic approaches is generally lacking in these rarer genetic epilepsies, particularly in those not associated with ion channel dysfunction. A stronger evidence base is required, and to generate this this will demand wide collaboration, and rigorous study design, and open access to pharmacogenomic data

Pilot study for subgroup classification for autism spectrum disorder based on dysmorphology and physical measurements in Chinese children

Poster Sessions: 157 - Comorbid Medical Conditions: abstract 157.058 58BACKGROUND: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder affecting individuals along a continuum of severity in communication, social interaction and behaviour. The impact of ASD significantly varies amongst individuals, and the cause of ASD can originate broadly between genetic and environmental factors. Objectives: Previous ASD researches indicate that early identification combined with a targeted treatment plan involving behavioural interventions and multidisciplinary therapies can provide substantial improvement for ASD patients. Currently there is no cure for ASD, and the clinical variability and uncertainty of the disorder still remains. Hence, the search to unravel heterogeneity within ASD by subgroup classification may provide clinicians with a better understanding of ASD and to work towards a more definitive course of action. METHODS: In this study, a norm of physical measurements including height, weight, head circumference, ear length, outer and inner canthi, interpupillary distance, philtrum, hand and foot length was collected from 658 Typical Developing (TD) Chinese children aged 1 to 7 years (mean age of 4.19 years). The norm collected was compared against 80 ASD Chinese children aged 1 to 12 years (mean age of 4.36 years). We then further attempted to find subgroups within ASD based on identifying physical abnormalities; individuals were classified as (non) dysmorphic with the Autism Dysmorphology Measure (ADM) from physical examinations of 12 body regions. RESULTS: Our results show that there were significant differences between ASD and TD children for measurements in: head circumference (p=0.009), outer (p=0.021) and inner (p=0.021) canthus, philtrum length (p=0.003), right (p=0.023) and left (p=0.20) foot length. Within the 80 ASD patients, 37(46%) were classified as dysmorphic (p=0.00). CONCLUSIONS: This study attempts to identify subgroups within ASD based on physical measurements and dysmorphology examinations. The information from this study seeks to benefit ASD community by identifying possible subtypes of ASD in Chinese population; in seek for a more definitive diagnosis, referral and treatment plan.published_or_final_versio

Proceedings of the 10th international conference on disability, virtual reality and associated technologies (ICDVRAT 2014)

The proceedings of the conferenc

Genes: Multigene Families, Control of Gene Expression, Genetic contributions to Human Diseases, including Chromosomal Fragile Sites and ‘Dynamic’ and ‘Non-self’ Mutations

The early work in this thesis utilizes the general approach of comparative analysis. In order to find out the relationship between entities (either functional or genetic) my colleagues and I have attempted to identify the important elements by detecting similarity between those entities that act in a similar manner. The philosophy behind this approach is simply that when two distinct objects perform a similar process then the requirements essential for that process will be revealed as similarities between those objects above a noise of difference between them. The use of comparative analysis in biological systems is an attempt to identify natural order from apparent chaos. This work includes but is not limited to :- 1. discovery of the family of kallikrein genes and exploration of their roles in biology, 2. identification of the DNA sequence elements required for hormonal and heavy metal control of metallothionein gene expression 3. discovery of at least some of the necessary and sufficient conditions for the appearance of fragile sites on chromosomes, and their consequent contributions to disease, 4. the molecular properties of repeat DNA sequence expansion that lead to dynamic mutation and consequent fragile site expression and / or disease pathogenesis. In a sense the use of genetic animal models in order to study gene function and pathogenesis follows similar logic of comparative analysis – the mutation of a single endogenous gene or the expression of a single introduced mutated gene in a (presumed) constant genetic background to enable the biological consequences of the genetic mutation or aberrant gene expression by comparing animals from the ‘wild-type’ or parent line with those that now carry the mutation or altered gene. This approach has been utilized in the most recent work contained herein as a means to determine gene function and / or to model human genetic disease pathogenesis, specifically pathogenic mechanisms of the protein WWOX in cancer and expanded repeat RNAs in neurodegenerative diseases. The culmination of this recent work is the development of an hypothesis – 4. that expanded repeat double-stranded RNA leads to neurodegeneration through its recognition by the RNA-binding pattern recognition receptors as a ‘non-self’ or foreign nucleic acid due to a paucity of RNA modification. The resultant pathogenic mechanism is therefore autoinflammatory disease. Given the wide range and variety of evidence of inflammatory activation in neurodegenerative diseases in general, this mechanism is therefore hypothesized to be the general causal mechanism for most (or all) of these diseases. A specific Introduction - highlighting the nature and significance of the work, and a Conclusion – of how this work has contributed to knowledge, are given at the start of each chapter, while the impact of the various components of this work is indicated by the number of citations for each of the included publications. Authorship contributions to each of the included publications in this work are also indicated with each specific reference.Thesis (DSc) -- University of Adelaide, School of Biological Sciences, 202