Cognitive modelling and control of human error processes in human-computer interaction with safety critical IT systems in telehealth.

The field of telehealth has developed rapidly in recent years. It provides medical support particularly to those who are living in remote areas and in emergency cases. Although developments in both technology and practice have been rapid, there are still many gaps in our knowledge with regard to the effective application of telehealth. This study investigated human colour perception in telehealth, specifically the colour red as one of the key symptoms when diagnosing different pathologies. The quality of medical images is safety critical when transmitting the symptoms of pathologies in telehealth, as distorted or degraded colours may result in errors. The study focused on the use of digital images in teleconsultation, particularly on images showing cellulitis (bacterial skin infection) and conjunctivitis (red eye) as case studies, as both of these pathologies involve the colour red in their diagnosis. The study proposed and tested the use of an image quality scale, which represented the level of image resolution; a red colour scale, which represented the intensity of redness in an image; and a confidence scale, which represented the levels of confidence that telehealth users had when judging the colour red. The research involved a series of experiments using hypothetico-deductive and formal hypothesis testing with two groups of participants, medical doctors and non-medical participants. The experiments were conducted in collaboration with the local National Health Service (NHS) Accident and Emergency (A&E) department at Aberdeen Royal Infirmary (ARI). Medical experts in ophthalmology and dermatology were also involved in selecting and verifying the relevant images. The study found that doctors and non-doctors were consistent in the majority of the experiments. The accuracy of the participants was demonstrably higher when using a colour scale with pictures, more so for the non-doctor group than the doctor group. It also found that the level of accuracy for both doctors and nondoctors was higher when using red colour scale of three divisions than when using a scale of five divisions. This result was supported by previous studies, which used telehealth for diagnosing extreme cases. The study also found that when the image quality was poor the participants had higher error rates and less consistency in their answers. The study found poor correlation between accuracy, confidence and time for both participant groups. The study found that most participants in both doctor and non-doctor groups had high confidence most of the time, whether the accuracy was high or low. It was also found that medical background or clinical experience had no effect on the accuracy level across the experiment sets. In some cases, doctors with no or little experience had higher accuracy than those with greater experience. This result may have significant implications for the feasibility of involving non-doctors in the management of telehealth systems, especially in tasks not requiring medical skills, such as colour classification. This has the potential to provide a considerable saving in resources and costs for healthcare providers. An auto-evaluation system was introduced, and proposed for further study, in order to improve the current telehealth diagnostic protocol and to avoid or prevent errors by making red colour classification more objective and accurate

Studies into the diagnosis, treatment and management of chlamydiosis in koalas

Koalas are an iconic Australian marsupial species that attract much public sympathy and support. Despite several thousand koalas being presented to wildlife rehabilitation facilities annually for treatment of traumatic injuries (primarily motor vehicle strikes and dog predation) and disease (principally chlamydiosis), little information exists regarding the success of treatments or whether rehabilitated animals survive in the wild after release. This thesis examines several aspects of the diagnosis, treatment and management of the most important infectious disease of koalas, chlamydiosis, and provides an evidence base for rational diagnostic and treatment decisions in the rehabilitation setting. Experimental work commences in Chapter 2 with a study of the admission records of a large koala rehabilitation facility (the Koala Hospital of the Koala Preservation Society of NSW) showing that traumatic presentations and those relating to clinical chlamydiosis were most common, with motor vehicle collisions apparently a significant and increasing threat to survival of the local koala population. The implications of these findings are discussed with reference to measures aimed at maintaining a viable population of wild koalas in Port Macquarie and for logistic planning at the Koala Hospital. Initial studies in this thesis confirmed that koalas with chlamydiosis are frequently treated at wildlife rehabilitation facilities. Despite the commonness of this disease, there is a lack of rigorous scientific studies examining frequently used treatments. Chapter 3, a retrospective review of medical records of a cohort of koalas admitted for treatment for chlamydiosis, revealed that diagnostic and treatment decisions were frequently based on clinical signs alone and treatment choices and durations were inconsistent with those used to successfully treat chlamydiosis in other species. Despite this, treated animals were frequently released and many survived in the wild. Chapter 4 outlines general methods common to the clinical work undertaken in Chapters 5, 7 and 9. Antibiotic treatment with drugs commonly used to treat chlamydiosis in other species (erythromycin, oxytetracycline) has led to wasting and death in koalas. A pilot study, presented in Chapter 5, found that, similarly, more modern forms of these drugs (doxycycline and azithromycin) cannot be used safely in koalas, leading to the author’s decision to investigate, in detail, the efficacy of the less conventional anti-chlamydial drugs, the fluoroquinolones. Studies of marsupial pharmacokinetics are uncommon and, prior to this thesis, there were no published studies of pharmacokinetics in koalas. The author’s investigations, using a modified agar diffusion assay (Chapter 6) and high performance liquid chromatography (Chapter 7), found the absorption of enrofloxacin and marbofloxacin by the oral route in koalas was extremely poor and suggested absorption rate limited disposition pharmacokinetics. In combination with plasma protein binding of approximately 50%, the concentrations of enrofloxacin and marbofloxacin achieved in plasma were not considered likely to inhibit the growth of chlamydial pathogens in vivo. In Chapter 8 the author explored the apparent contradiction between the failure to achieve appropriate plasma concentrations of fluoroquinolones to treat chlamydiosis and the apparent efficacy of these drugs reported in historical medical records. Methods to monitor clinical signs by clinical scoring and chlamydial load using real-time polymerase chain reaction were developed during the study. The results of these studies showed that clinical signs were poorly sensitive in determining the presence of chlamydial organisms in koalas; all fluoroquinolone treatment regimes led to a dramatic reduction in Chlamydophila pecorum load during treatment; and clinical signs improved in many animals. Importantly, however, pathogen load rebounded after withdrawal of treatment, indicating that most animals failed to clear infections. These findings have implications for the diagnosis, and treatment of chlamydial disease in koalas and for the subsequent return of fluoroquinolone treated animals to the wild. The findings and limitations of these studies are presented in general terms in Chapter 9 and recommendations for future studies are proposed

Current Concepts in Zika Research

Zika is an arboviral disease that has caused a significant impact, especially in the Americas after the epidemics in 2015 and 2016. The World Health Organization (WHO) declared it as a Public Health Emergency of International Concern (PHEIC) in 2016, linking it with the Guillain-Barré syndrome and especially the microcephaly and the Congenital Zika Syndrome. The multiple consequences, especially in the central and peripheral nervous system in the short and long term, are still to be better defined. Therefore research on Zika is crucial. This book presents an update of the significant epidemiological and clinical research of Zika over the last years in many aspects and from a multinational perspective

Colorado State University, College of Veterinary Medicine and Biomedical Sciences, 11th annual CVMBS research day scientific proceedings

Includes the Pfizer Research Award winner and abstracts only of the oral sessions and posters

Microbiology for Allied Health Students

This open textbook is a remix of Openstax Microbiology, CC-BY 4.0, and created through an Affordable Learning Georgia Round Six Textbook Transformation Grant. The textbook has the following supplemental materials within this repository: This is a collection of instructional materials for the following open textbook and lab manual: Microbiology for Allied Health Students Lab Manual Microbiology for Allied Health Students Instructional Materials Authors\u27 Description: Microbiology for Allied Health Students is designed to cover the scope and sequence requirements for the single semester Microbiology course for non-majors and allied health students. The book presents the core concepts of microbiology with a focus on applications for careers in allied health. The pedagogical features of Microbiology for Allied Health Students make the material interesting and accessible to students while maintaining the career-application focus and scientific rigor inherent in the subject matter. The scope and sequence of Microbiology for Allied Health Students has been developed and vetted with input from numerous instructors at institutions across the U.S. It is designed to meet the needs of most microbiology courses allied health students. With these objectives in mind, the content of this textbook has been arranged in a logical progression from fundamental to more advanced concepts. The opening chapters present an overview of the discipline, with individual chapters focusing on cellular biology as well as each of the different types of microorganisms and the various means by which we can control and combat microbial growth. The focus turns to microbial pathogenicity, emphasizing how interactions between microbes and the human immune system contribute to human health and disease. The last several chapters of the text provide a survey of medical microbiology, presenting the characteristics of microbial diseases organized by body system. Accessible files with optical character recognition (OCR) and auto-tagging provided by the Center for Inclusive Design and Innovation.https://oer.galileo.usg.edu/biology-textbooks/1015/thumbnail.jp

Studies on the Pathogenesis of Trachomatous Scarring

Trachoma is a chronic keratoconjunctivitis caused by recurrent episodes of infection with the gram negative bacterium Chlamydia trachomatis. It is the most common infectious cause of blindness with at least 1.3 million estimated to be blind from the disease, 8 million to have trichiasis and 40 million to have active disease. Trachoma is now predominantly found in poor, rural areas in developing countries and it is classified by the World Health Organization as a Neglected Tropical Disease. Ocular infection with C. trachomatis is usually found in children and causes a marked inflammatory response with a follicular conjunctivitis and papillary hypertrophy. After suffering recurrent episodes of infection and inflammation these children are at risk of developing conjunctival scarring which can progress to entropion, trichiasis, corneal opacity and blindness in later life. The pathogenesis of the scarring process is believed to be immune mediated but is poorly understood. The aim of this work was to further our understanding of the pathogenesis of scarring trachoma. Two case-control studies were undertaken. The Trachomatous Scarring (TS) study included 363 cases with mild-moderate conjunctival scarring and 363 control subjects. Participants underwent a clinical examination, digital photography, in vivo confocal microscopy (IVCM) and had conjunctival swabs taken for quantitative gene expression, C. trachomatis detection and bacteriological culture. The Trachomatous Trichiasis (TT) study included 34 cases with trachomatous trichiasis who had severe conjunctival scarring and 33 control subjects. Participants underwent similar examination and sample collection procedures as those in the TS study, but in addition had conjunctival biopsy samples taken for histology and immunohistochemistry. Scarring was associated with evidence of an innate immune response with increased expression of antimicrobial peptides and pro-inflammatory mediators. Confirmation of an innate response was seen with immunohistochemistry with an increased infiltrate of Natural Killer cells seen in scarred tissue. Immunohistochemistry also showed an infiltrate of unidentified CD45 negative cells in cases. Scarring was associated with differential regulation of various modifiers of the extra-cellular matrix. There was no evidence of a Th2 response in scarred cases, but rather a Th1 response was detected. Non-chlamydial bacterial infection was more frequently found in cases than controls and was also associated with upregulation of innate and pro-inflammatory mediators. C. trachomatis was very rarely detected, but when seen was associated with a characteristic Th1 response seen in children. Connective tissue scarring could be seen morphologically with masked grading of IVCM and histological sections. An increased inflammatory cell infiltrate could also be seen with both examination techniques. Gene expression changes in relation to IVCM scarring generally showed good agreement with corresponding changes by clinical scarring. IVCM appeared to be able to detect subclinical scarring and also identified dendritifrom cells which were strongly associated with the presence of scarring. This work confirms other studies highlighting the importance of innate immune responses in the pathogenesis of trachomatous scarring. Non-chlamydial bacterial infection may be an important factor in driving this innate response with resulting tissue damage and fibrosis. Tissue changes could be objectively assessed with IVCM for various parameters, especially connective tissue scarring, and allowed some novel observations about the scarring process to be made

Clinical and experimental studies on the cellular mediators of corneal allograft rejection

Despite significant advances in our knowledge of the cellular and molecular elements of transplant immunology the 10 year survival probability for all human corneal grafts is 0.73. In some "high-risk" recipients it is as low as 0.37. To date almost all our knowledge about the cellular events during acute corneal graft rejection comes from animal models. In mice, the presence of pre-existing host corneal vascularisation confers "high-risk" status on a graft and has been shown to accelerate rejection. In the first part of this thesis the effect on survival of grafting to an inflamed conjunctival bed was investigated. Using a mouse model of allergic conjunctivitis significantly reduced survival was seen in graft recipients with perioperative conjunctival inflammation. This appeared to be due to the local effects of conjunctivitis rather than systemic effects of allergy/ atopy. Subsequent experiments investigated the effect of perioperative allergic conjunctivitis on the cellular components of both early (surgical trauma-induced, alloantigen-independent) and late (alloantigen-dependent; rejection) post-keratoplasty anterior segment inflammation and demonstrated significant effects on both. Grafts recipients with allergic conjunctivitis had significantly greater early post-operative corneal inflammation and associated corneal and conjunctival lymphangiogenesis. Analysis of graft infiltrating cells during rejection in mice confirmed that large numbers of CD4+ cells, CD8+ cells and macrophages were recruited. Flow cytometric analysis of human aqueous during acute endothelial rejection demonstrated for the first time the presence of CD4+ cells, CD8+ cells and a surprisingly high proportion of macrophages therein. In mouse recipients with allergic conjunctivitis eosinophils were found in both the graft itself and the ciliary body during rejection although the role of these cells during rejection is uncertain. Chemokine analysis during both murine and human corneal graft rejection demonstrated increased expression of the chemokine IP-10 (CXCL-10) suggesting a potentially important role for this protein in the rejection process

The development and application of protemics to the analysis of Chlamydia Trachomatis

The bacterial pathogen Chlamydia trachomatis causes Trachoma, the worlds leading cause of preventable blindness and is also responsible for the most common curable sexually transmitted disease in the UK and United States. C. trachomatis is an obligate intracellular organism characterised by a unique and complex growth cycle. Its study presents many challenges since it has historically been recalcitrant to genetic manipulation and growth in the absence of a host cell. Nevertheless, the sequencing of the C. trachomatis genome and its relatively small size by comparison to genomes from other bacterial pathogens, has paved the way for studies at the proteomic level.This thesis describes the development and application of proteomic approaches to study C. trachomatis L2. To survey the expressed chlamydial proteome, a combination of the qualitative approaches, 2-DGE, MudPIT and GeLC-MS/MS; and the quantitative approaches AQUA, iTRAQ and LC-MSE were used. Collectively, the approaches efficiently identified 648 expressed proteins, representing ~72% of the predicted proteome of C. trachomatis L2, from both the infectious (elementary body, EB) and replicating (reticulate body, RB) form of the pathogen. In the infectious EB, the entire set of predicted glycolytic enzymes were detected, indicating that metabolite flux rather than de novo synthesis of this pathway is triggered upon infection of host cells. Further, proteomic analysis of the RB form also uncovered biosynthetic enzymes for chlamydial cell wall synthesis, indicating that peptidoglycan is produced in some form during growth in host cells. Comparison of the quantitative approaches iTRAQ and LC-MSE demonstrated that LC-MSE quantitative data was significantly more robust and extensive relative to iTRAQ data. In addition to information on relative amounts of these proteins between the two forms, LC-MSE data also yielded the cellular concentration (molecules per cell) for 489 proteins.This extensive set of absolute quantitation data permits estimates of the energy invested in the synthesis of various classes of proteins. The results indicate that C. trachomatis devotes most of its energy into maintenance of the translational machinery. However, it also expends significant amounts of energy into making cell envelope components and a set of hitherto hypothetical proteins. These proteins, which account for the bulk of the energy invested by the intracellular RB form of the pathogen as it converts to the extracellular EB form, highlight the importance of absolute quantitation data for understanding the biological processing status of the cell. The datasets also revealed a large number of proteins that were differentially expressed between replicating RBs and infectious EBs, ranging from 8.4-fold down-regulation to 3.5-fold up-regulation. Consistent with transcriptomic studies (Belland et al., 2003), proteins involved in protein synthesis, ATP generation, central metabolism, secretion and nutrient uptake were predominant in the metabolically active RB at 15 h PI. Although many of the proteins in these functional categories were down-regulated in EBs, proteins required for glycolysis, central metabolism, protein synthesis, and type III secretion were present in significant amounts in EBs suggesting that the infectious EB is primed ‘ready-to-go’ upon contact with the host cell

Lateral Flow Nucleic Acid Biosensor for the Detection of Sexually Transmitted Diseases

Nucleic acid detection is of central importance for the diagnosis and treatment of genetic diseases, infectious agents, bio-warfare agents, and drug discovery. Nucleic acid testing for diseases is exclusively performed in laboratories using high-end instrumentation and personnel. However, this has developed the need for point of care diagnostics which can provide near-patient testing in a clinic, doctor’s office, or home. Such diagnostic tools can prove advantageous when rapid response is required or when suitable facilities are unavailable. Compared to equivalent methods used in laboratories, point of care testing is more affordable, as it eliminates the need for expensive instrumentation and skilled labor. One option involves the use of lateral flow assays. Pre-fabricated strips of dry reagents activated upon fluid application are already used in diagnostics, such as to ascertain pregnancy. Nucleic acid based detection assays on lateral flow offer several advantages over traditional microbiological detection methods. In this work we introduce a lateral flow biosensor that can combine the optical properties of nanoparticles (such as gold nanoparticles) with conventional immunoassay techniques to deliver a simple platform for rapid analysis of DNA with high sensitivity and selectivity. The quick 30 minute assay provides a platform to detect multiple nucleic acids with high efficiency achieved via chromatographic separation sandwich-type DNA hybridization reactions. Captured gold nanoparticles on the device can provide qualitative analysis by observing the color change to red and a semi-quantitative analysis via a strip reader. The biosensor was applied to the detection of human genomic DNA directly with high sensitivity and selectivity. The work was further expanded to detect Chlamydia trachomatis and Neisseria gonorrhoeae samples using nucleic acid amplification to generate large numbers of target copies. Improvements were made in the preparation of the biosensor to enable detection of Human Papilloma Virus Type-16. The clinical samples obtained were amplified using PCR for direct detection on the lateral flow biosensor without interference from other HPV types (e.g. HPV 18). The feasibility of the biosensor shows great potential for further development to assure its use in point of care diagnosis. The promising properties of the biosensor are reported in this dissertation

Topical Ocular Delivery to Posterior Eye Tissues

Treatment of diseases affecting the posterior segment of the eye with intravitreal injections of drugs are effective yet invasive and associated with side effects such as retinal detachment and endophthalmitis. Rapamycin (RAP) was explored in eye research for chronic inflammatory disorders such as posterior uveitis. Tacrolimus (TAC) suspension is used to treat moderate to severe atopic keratoconjunctivitis (AKC) and vernal keratoconjunctivitis (VKC). This study's objectives were to formulate the hydrophobic compounds: RAP and TAC in aqueous eye drop formulations, with the overall aim of using these formulations to treat posterior uveitis, AKC and VKC, respectively. A thin-film hydration method was used to encapsulate RAP and TAC within the chitosan-based amphiphile: N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan (GCPQ). The formulations were characterised, and their stability studied under three storage conditions for one month. The biocompatibility of GCPQ was assessed by measuring the IC50 value in a standard MTT assay. Experimental autoimmune uveitis (EAU) was used as a mice model to explore how RAP would clinically function on retinal disease. The ocular biodistribution of the formulations was studied in healthy rabbits, and LC-MS/MS analysed the ocular tissues. Nanoparticles formulations (GCPQ: RAP, 0.2% w/v) and (GCPQ: TAC, 0.1% w/v) were produced with characteristics within the ocular comfort range. The formulations were stable on refrigeration for one month. GCPQ demonstrates good biocompatibility in vitro with IC50 ranging from 0.44–4.5 mg/mL. On topical application in vivo, GCPQ delivered RAP to the rabbit choroid-retina one-hour post-dosing at concentration 145±49 ng/g of tissue. The topical application of GCPQ: RAP 0.2% w/v on EAU mice model suppressed the disease progression. The TAC concentrations in rabbit cornea and conjunctiva one-hour post-dosing were 4452±2289 and 516±180 ng/g of tissue, respectively. A topical ocular aqueous RAP and TAC eye drop formulations have been prepared with the ability to deliver sufficient drugs to the relevant ocular surface tissues