Modeling, Design and Test of an Integrated Optical Neural Recording Device

It has long been a goal of neuroscientists to understand how electrophysiological activity in the nervous system corresponds to, and causes, specific physiological actions. Such knowledge could be used to develop cures for disabilities related to nervous system dysfunction, and to control artificial limbs or restore motion to a paralyzed patient. This has motivated research into technologies, broadly termed brain-machine interfaces, for interfacing with the nervous system. One category of such neural interfaces is implantable neural recording devices, which monitor and record neural signals through a microelectronic device implanted in the body. Typical implantable neural recording devices use a micro-electrode array to record electrical signals simultaneously from a multitude of neurons. Unfortunately, devices employing micro-electrode arrays have several issues from both the biological and circuit design points of view. These issues include tissue damage due to implantation of a micro-electrode array, degradation of recording fidelity over time, limited spatial resolution, the requirement to maintain charge balance in tissue, and the difficulty in implementing low-frequency (large time constant) filter cutoffs with limited chip area. These issues provided the motivation to investigate alternative methods for neural recording - namely optical methods based on fluorescence detection with voltage-sensitive fluorescent proteins. Optical recording methods can alleviate many of the issues with electrical recording, as well as provide other advantages, such as recording targeted to specific neurons/neuron types and higher spatial resolution due to reduced recording site pitch. The major limitations of fully implantable optical recording devices stem from size constraints, the attenuation of light in tissue, which limits imaging depth, and the need for genetically programmed voltage-sensitive fluorescent proteins, which must be introduced to the tissue in the case of chronic recording. This research began with investigating the feasibility of replacing an electrical neural record- ing front end with an optical front end - the conclusion being that producing an initial design was worthwhile. Thus, this thesis presents a prototype optical neural recording device for detecting individual spikes in Layer I of the brain. The device is designed for the fully implantable scenario, where space for typical fluorescence imaging optical components is limited, and a high level of integration is required. The thesis describes: 1) Modeling: a general framework for modeling near-field fluorescence detection systems is presented; the model is then extended and applied to the design of the optical neural recording device for detecting individual spikes in Layer I of the brain, taking into account light attenuation in tissue; 2) Design: the design of a high-sensitivity CMOS imaging chip used in the device; 3) Packaging: the packaging of the CMOS imager with LED dies and an excitation filter; and 4) Testing: the experimental results from testing the packaged device with a fluorescent tissue phantom designed to emulate layer I of the brain. Ideas for future work on such devices are discussed

An experimental investigation of heating mechanisms, mode transition and instabilities in a radio frequency inductively coupled plasma

Radio frequency (RF) inductively coupled plasma (ICP) have been known and studied for over a century In recent years, due to the vast array of potential applications of plasma technology, research in the area has become more prolific. This thesis presents the results of a detailed experimental investigation that uses electrical diagnostics (Langmuir and magnetic field (5 ) probes etc ) on a particular type of inductively coupled plasma source (re-entrant cavity). The investigation focuses on three aspects of the ICP Firstly the heating mechanisms that sustain the plasma are characterized. It is found that the RF electric field and current density distributions determined from B probe measurements indicate a strong anomalous skin effect. This is exemplified by non-monotomc decay of the electromagnetic fields, phase reversal and bifurcation, as well as negative power absorption regions. These features are interpreted m terms of spatial dispersion of the conductivity due to the electron thermal motion at low pressure. Secondly the E-H mode transition is comprehensively investigated using various steady state and time resolved diagnostics, the results show that hysteresis with respect to the transition current is accounted for by variation in the plasma production efficiency due to changes in the electron energy distribution function (EEDF) and the presence of metastable atoms Finally, a specific type of instability observed in low pressure ICPs is investigated experimentally and the results are found to agree on many points with a proposed model describing the instability

Genetic Variation in Clinical Varicella-Zoster Virus Isolates Collected in Ireland Between 2002 and 2003

Analysis of genetic variation in 16 varicella-zoster virus (VZV) isolates selected at random and circulating in the Irish population between March 2002 and February 2003 was carried out. A 919 bp fragment of the glycoprotein E gene (open reading frame 68) encompassing codon 150, at which a non-synonymous mutation defines the escape mutant VZV-MSP, and including two other epitope regions e1 and c1, was sequenced. No new single nucleotide polymorphisms (SNPs) were detected, indicating stability of these epitopes in clinical isolates of VZV. However, when four informative polymorphic markers consisting of defined regions from genes 1, 21, 50, and 54 were sequenced 14 variable nucleotide positions were identified. Phylogenetic analysis showed the presence of three highly supported clades A, B, and C circulating in the Irish population. Approximately one third (6/16; 37.5%) of the Irish VZV isolates in this study belonged to genotype C, 4/16 (25%) to genotype A, and 4/16 (25%) to genotype B. A smaller number 2/16 (12.5%) belonged to genotype J1. This indicates remarkable heterogeneity in the Irish population given the small sample size. No evidence was found to suggest any of the 16 isolates was a recombinant. These findings have implications for the model of geographic isolation of VZV clades to certain regions as the circulating Irish VZV population appears to comprise approximately equal numbers of each of the main genotypes. This data is inconsistent with a model of strict geographical separation of VZV genotypes and suggests that VZVdiversity ismorepronounced in certain areas than had been thought previously

Estimation of Train Driver Workload: Extracting Taskload Measures from On-Train-Data-Recorders

This paper presents a method to extract train driver taskload from downloads of on-train-data-recorders (OTDR). OTDR are in widespread use for the purposes of condition monitoring of trains, but they may also have applications in operations monitoring and management. Evaluation of train driver workload is one such application. The paper describes the type of data held in OTDR recordings and how they can be transformed into driver actions throughout a journey. Example data from 16 commuter journeys are presented, which highlights the increased taskload during arrival at stations. Finally, the possibilities and limitations of the data are discussed

Genetic Variation in Clinical Varicella-Zoster Virus Isolates Collected in Ireland Between 2002 and 2003

Analysis of genetic variation in 16 varicella-zoster virus (VZV) isolates selected at random and circulating in the Irish population between March 2002 and February 2003 was carried out. A 919 bp fragment of the glycoprotein E gene (open reading frame 68) encompassing codon 150, at which a non-synonymous mutation defines the escape mutant VZV-MSP, and including two other epitope regions e1 and c1, was sequenced. No new single nucleotide polymorphisms (SNPs) were detected, indicating stability of these epitopes in clinical isolates of VZV. However, when four informative polymorphic markers consisting of defined regions from genes 1, 21, 50, and 54 were sequenced 14 variable nucleotide positions were identified. Phylogenetic analysis showed the presence of three highly supported clades A, B, and C circulating in the Irish population. Approximately one third (6/16; 37.5%) of the Irish VZV isolates in this study belonged to genotype C, 4/16 (25%) to genotype A, and 4/16 (25%) to genotype B. A smaller number 2/16 (12.5%) belonged to genotype J1. This indicates remarkable heterogeneity in the Irish population given the small sample size. No evidence was found to suggest any of the 16 isolates was a recombinant. These findings have implications for the model of geographic isolation of VZV clades to certain regions as the circulating Irish VZV population appears to comprise approximately equal numbers of each of the main genotypes. This data is inconsistent with a model of strict geographical separation of VZV genotypes and suggests that VZVdiversity ismorepronounced in certain areas than had been thought previously

Pneumonia failing to respond to treatment

SummaryHerpes simplex virus type 1 (HSV-1) is frequently isolated from the respiratory tract of critically ill patients. However, diagnosis of clinically significant HSV-1 pneumonia is difficult as the presentation is non-specific and there is no diagnostic reference standard to differentiate from non-infectious contamination.We present a case of HSV-1 pneumonia in a young asthmatic patient who was potentially immunocompromised through long-term corticosteroid usage. The quantitative PCR titre from bronchoalveolar lavage fluid was high (9×103copies/ml) and the patient made a dramatic clinical and radiographic recovery upon treatment with acyclovir. We suggest that similar PCR levels in the appropriate clinical setting should prompt consideration of anti-viral therapy

Inkjet Printable Organic-Inorganic Hybrids Based On Polyaniline

Polyaniline (PANI) is an organic polymer that has generated significant interest as an electrically conductive material component, and is used in applications such as sensors and flexible displays. A significant number of PANI-based devices have been prepared using inkjet printing; a fabrication technique favoured for its additive patterning ability and its efficient use of material. Combining precious metals and conducting organic polymers through compositing provides combinatorial materials, potentially possessing both the properties of the metallic component and the conducting polymer, as well as unique ensuing properties due to the compositing itself. The type of research is critical for driving innovation in materials research. Exploiting an established oxidative polymerisation protocol for producing stable nanodispersions of PANI was used where the standard oxidant was replaced with HAuCl4 or AgNO3 at a range of monomer:oxidant ratios to produce a range of composite dispersions. The morphology and populations of the metallic structures (including spherical nanoparticles and nano-whiskers), as well as the quality of the PANI were shown to be influenced by the concentration and type of oxidant used. This area of research is currently in its infancy where the research is focusing on demonstrating composite synthesis rather than the application of these materials for device fabrication. However, anticipated applications of these composite materials include noble metal deposition, electro-catalysis, neural tissue engineering, sensors, photovoltaic cells and memory devices

Fourteen Draft Genome Sequences for the First Reported Cases of Azithromycin-Resistant Neisseria gonorrhoeae in Ireland

Here, we report the draft genome assemblies of 14 azithromycin-resistantNeisseria gonorrhoeaeclinical isolates, representing the first such strains identified in Ireland. Among these isolates are the first reported highly resistant strains (MIC >256mg/liter), which both belonged to the ST1580 sequence type

Public health surveillance of multidrug-resistant clones of Neisseria gonorrhoeae in Europe: a genomic survey.

BACKGROUND: Traditional methods for molecular epidemiology of Neisseria gonorrhoeae are suboptimal. Whole-genome sequencing (WGS) offers ideal resolution to describe population dynamics and to predict and infer transmission of antimicrobial resistance, and can enhance infection control through linkage with epidemiological data. We used WGS, in conjunction with linked epidemiological and phenotypic data, to describe the gonococcal population in 20 European countries. We aimed to detail changes in phenotypic antimicrobial resistance levels (and the reasons for these changes) and strain distribution (with a focus on antimicrobial resistance strains in risk groups), and to predict antimicrobial resistance from WGS data. METHODS: We carried out an observational study, in which we sequenced isolates taken from patients with gonorrhoea from the European Gonococcal Antimicrobial Surveillance Programme in 20 countries from September to November, 2013. We also developed a web platform that we used for automated antimicrobial resistance prediction, molecular typing (N gonorrhoeae multi-antigen sequence typing [NG-MAST] and multilocus sequence typing), and phylogenetic clustering in conjunction with epidemiological and phenotypic data. FINDINGS: The multidrug-resistant NG-MAST genogroup G1407 was predominant and accounted for the most cephalosporin resistance, but the prevalence of this genogroup decreased from 248 (23%) of 1066 isolates in a previous study from 2009-10 to 174 (17%) of 1054 isolates in this survey in 2013. This genogroup previously showed an association with men who have sex with men, but changed to an association with heterosexual people (odds ratio=4·29). WGS provided substantially improved resolution and accuracy over NG-MAST and multilocus sequence typing, predicted antimicrobial resistance relatively well, and identified discrepant isolates, mixed infections or contaminants, and multidrug-resistant clades linked to risk groups. INTERPRETATION: To our knowledge, we provide the first use of joint analysis of WGS and epidemiological data in an international programme for regional surveillance of sexually transmitted infections. WGS provided enhanced understanding of the distribution of antimicrobial resistance clones, including replacement with clones that were more susceptible to antimicrobials, in several risk groups nationally and regionally. We provide a framework for genomic surveillance of gonococci through standardised sampling, use of WGS, and a shared information architecture for interpretation and dissemination by use of open access software. FUNDING: The European Centre for Disease Prevention and Control, The Centre for Genomic Pathogen Surveillance, Örebro University Hospital, and Wellcome