Novel digital biomarkers for frontotemporal dementia

Frontotemporal dementia (FTD) is a heterogenous neurodegenerative disease and is caused by an autosomal dominant mutation in around one third of cases. This pattern of inheritance enables FTD to be studied in the presymptomatic phase, where individuals carry the genetic mutation but have yet to develop symptoms. There are currently no approved treatments for FTD, although clinical trials aiming to target interventions at the earliest disease stage, are underway. There is an urgent need for biomarkers that can reliably detect and monitor the progression of disease in the presymptomatic period, though there are a distinct lack of sensitive cognitive measures. This thesis aims to establish the validity and sensitivity of a set of digital biomarkers that can be used to measure cognitive function in FTD. I begin this thesis by describing the Ignite computerised cognitive assessment, developing normative properties for the tests through a remote data collection study in over 2,000 healthy controls. I build upon this validation by establishing the concurrent validity of Ignite with gold-standard pen and paper tasks, the test-retest reliability upon repeated administration, and demonstrate the tests are sensitive to presymptomatic impairment across several cognitive domains. I also describe a novel portable eye tracking experiment that can be completed outside of the lab, first highlighting the validity of the tests as measures of cognitive function and demonstrating their sensitivity in detecting early changes in social cognition in the presymptomatic period. Finally, I investigate a smartphone app that passively monitors human-device interactions to generate digital biomarkers of cognitive function. I establish the acceptability of the app in the general population before demonstrating the measures produced can detect differences in keyboard interactions in presymptomatic FTD mutation carriers. This work provides evidence that biomarkers generated from different digital devices are valid and sensitive measures of cognitive impairment in FTD. Therefore, digital biomarkers could replace outdated pen and paper tasks and be used as outcome measures in clinical trials

Simulation of Three Dimensional Electrostatic Field Configuration in Wire Chambers : A Novel Approach

Three dimensional field configuration has been simulated for a simple wire chamber consisting of one anode wire stretched along the axis of a grounded square cathode tube by solving numerically the boundary integral equation of the first kind. A closed form expression of potential due to charge distributed over flat rectangular surface has been invoked in the solver using Green's function formalism leading to a nearly exact computation of electrostatic field. The solver has been employed to study the effect of several geometrical attributes such as the aspect ratio ($\lambda = \frac{l}{d}$, defined as the ratio of the length $l$ of the tube to its width $d$) and the wire modeling on the field configuration. Detailed calculation has revealed that the field values deviate from the analytic estimates significantly when the $\lambda$ is reduced to 2 or below. The solver has demonstrated the effect of wire modeling on the accuracy of the estimated near-field values in the amplification region. The thin wire results can be reproduced by the polygon model incorporating a modest number of surfaces ($\geq 32$) in the calculation with an accuracy of more than 99%. The smoothness in the three dimensional field calculation in comparison to fluctuations produced by other methods has been observed.Comment: Revised version submitted to Elsevier Science including some more near-field calculation

Reflective scattering effects in double-pomeron exchange processes

We discuss energy dependence of rapidity gap survival probability in the double-pomeron exchange processes with account of the reflective scattering effects.Comment: 11 pages, 3 figure

Study protocol: computerised cognitive testing in a cohort of people with frontotemporal dementia

Introduction: The term frontotemporal dementia (FTD) refers to a heterogeneous group of neurodegenerative disorders affecting the frontal and temporal lobes. Cognitively, impairment of executive function and social cognition predominates across the FTD spectrum, although other domains can be affected. Traditionally, cognition is tested through standard ‘pen and paper’ tasks in FTD. However, recent attempts have been made across other neurodegenerative disorders such as Alzheimer’s disease to develop computerised batteries that allow more accurate and sensitive detection of cognitive impairment. / Methods and analysis: This paper describes the development of a novel battery of tests for a tablet computer, particularly focused on FTD. It consists of 12 different tasks which aim to tap into information processing speed, various aspects of executive function, social cognition, semantic knowledge, calculation and visuospatial skills. Future studies will focus on validating the battery in a healthy control cohort, comparing it against a standard ‘pen and paper’ psychometric battery, and finally testing it within an FTD cohort, including those with genetic forms of FTD where we will be able to assess its ability to detect very early cognitive deficits prior to the onset of symptoms. / Ethics and dissemination: Normative data will be produced in the initial validation study (approved by the UCL Ethics Committee, project ID 17691/002) and will be made available online

An Iterative and Toolchain-Based Approach to Automate Scanning and Mapping Computer Networks

As today's organizational computer networks are ever evolving and becoming more and more complex, finding potential vulnerabilities and conducting security audits has become a crucial element in securing these networks. The first step in auditing a network is reconnaissance by mapping it to get a comprehensive overview over its structure. The growing complexity, however, makes this task increasingly effortful, even more as mapping (instead of plain scanning), presently, still involves a lot of manual work. Therefore, the concept proposed in this paper automates the scanning and mapping of unknown and non-cooperative computer networks in order to find security weaknesses or verify access controls. It further helps to conduct audits by allowing comparing documented with actual networks and finding unauthorized network devices, as well as evaluating access control methods by conducting delta scans. It uses a novel approach of augmenting data from iteratively chained existing scanning tools with context, using genuine analytics modules to allow assessing a network's topology instead of just generating a list of scanned devices. It further contains a visualization model that provides a clear, lucid topology map and a special graph for comparative analysis. The goal is to provide maximum insight with a minimum of a priori knowledge.Comment: 7 pages, 6 figure

Basal forebrain atrophy in frontotemporal dementia

Background: The basal forebrain is a subcortical structure that plays an important role in learning, attention, and memory. Despite the known subcortical involvement in frontotemporal dementia (FTD), there is little research into the role of the basal forebrain in this disease. We aimed to investigate differences in basal forebrain volumes between clinical, genetic, and pathological diagnoses of FTD. / Methods: 356 patients with FTD were recruited from the UCL Dementia Research Centre and matched on age and gender with 83 cognitively normal controls. All subjects had a T1-weighted MR scan suitable for analysis. Basal forebrain volumes were calculated using the Geodesic Information Flow (GIF) parcellation method and were compared between clinical (148 bvFTD, 82 svPPA, 103 nfvPPA, 14 PPA-NOS, 9 FTD-MND), genetic (24 MAPT, 15 GRN, 26 C9orf72) and pathological groups (28 tau, 3 FUS, 35 TDP-43) and controls. A subanalysis was also performed comparing pathological subgroups of tau (11 Pick's disease, 6 FTDP-17, 7 CBD, 4 PSP) and TDP-43 (12 type A, 2 type B, 21 type C). / Results: All clinical subtypes of FTD showed significantly smaller volumes than controls (p≤ 0.010, ANCOVA), with svPPA (10% volumetric difference) and bvFTD (9%) displaying the smallest volumes. Reduced basal forebrain volumes were also seen in MAPT mutations (18%, p<0.0005) and in individuals with pathologically confirmed FTDP-17 (17%), Pick's disease (12%), and TDP-43 type C (8%) (p<0.001). / Conclusion: Involvement of the basal forebrain is a common feature in FTD, although the extent of volume reduction differs between clinical, genetic, and pathological diagnoses. Tauopathies, particularly those with MAPT mutations, had the smallest volumes. However, atrophy was also seen in those with TDP-43 type C pathology (most of whom have svPPA clinically). This suggests that the basal forebrain is vulnerable to multiple types of FTD-associated protein inclusions

Novel phytosynthesis of nanoparticles using Indigeneous Australian Plants

Nanoparticles are considered to be the building blocks of nanotechnology. Biosynthesis of nanoparticles using plant material is an exciting and relatively new developing research area in nanobiotechnology. In the present study, Eucalyptus leaves were collected from Olive pink botanical garden, Alice Springs, Australia and were used to synthesize silver nanoparticles. Cubical structured and well monodispersed silver nanoparticles were formed with an average size of 50nm. The formed silver nanoparticles are found to have promising applications in medicine as good antimicrobial agents. To the best of our knowledge this is the first report on exploiting indigeneous Australian plant sources for the synthesis of metallic nanoparticles