Parallel definition of tear film maps on distributed-memory clusters for the support of dry eye diagnosis

[Abstract] Background and objectives The analysis of the interference patterns on the tear film lipid layer is a useful clinical test to diagnose dry eye syndrome. This task can be automated with a high degree of accuracy by means of the use of tear film maps. However, the time required by the existing applications to generate them prevents a wider acceptance of this method by medical experts. Multithreading has been previously successfully employed by the authors to accelerate the tear film map definition on multicore single-node machines. In this work, we propose a hybrid message-passing and multithreading parallel approach that further accelerates the generation of tear film maps by exploiting the computational capabilities of distributed-memory systems such as multicore clusters and supercomputers. Methods The algorithm for drawing tear film maps is parallelized using Message Passing Interface (MPI) for inter-node communications and the multithreading support available in the C++11 standard for intra-node parallelization. The original algorithm is modified to reduce the communications and increase the scalability. Results The hybrid method has been tested on 32 nodes of an Intel cluster (with two 12-core Haswell 2680v3 processors per node) using 50 representative images. Results show that maximum runtime is reduced from almost two minutes using the previous only-multithreaded approach to less than ten seconds using the hybrid method. Conclusions The hybrid MPI/multithreaded implementation can be used by medical experts to obtain tear film maps in only a few seconds, which will significantly accelerate and facilitate the diagnosis of the dry eye syndrome.Ministerio de Economía y Competitividad; TIN2013-42148-PPortugal. Fundação para a Ciência e a Tecnologia; POCI-01-0145-FEDER-006961Portugal. Fundação para a Ciência e a Tecnologia; UID/EEA/50014/2013Portugal. Fundação para a Ciência e a Tecnologia; SFRH/BPD/111177/2015

Development of Novel Diagnostic Tools for Dry Eye Disease using Infrared Meibography and In Vivo Confocal Microscopy

Dry eye disease (DED) is a multifactorial disease of the ocular surface where tear film instability, hyperosmolarity, neurosensory abnormalities, meibomian gland dysfunction, ocular surface inflammation and damage play a dedicated etiological role. Estimated 5 to 50% of the world population in different demographic locations, age and gender are currently affected by DED. The risk and occurrence of DED increases at a significant rate with age, which makes dry eye a major growing public health issue. DED not only impacts the patient’s quality of vision and life, but also creates a socio-economic burden of millions of euros per year. DED diagnosis and monitoring can be a challenging task in clinical practice due to the multifactorial nature and the poor correlation between signs and symptoms. Key clinical diagnostic tests and techniques for DED diagnosis include tearfilm break up time, tear secretion – Schirmer’s test, ocular surface staining, measurement of osmolarity, conjunctival impression cytology. However, these clinical diagnostic techniques are subjective, selective, require contact, and are unpleasant for the patient’s eye. Currently, new advances in different state-of-the-art imaging modalities provide non-invasive, non- or semi-contact, and objective parameters that enable objective evaluation of DED diagnosis. Among the different and constantly evolving imaging modalities, some techniques are developed to assess morphology and function of meibomian glands, and microanatomy and alteration of the different ocular surface tissues such as corneal nerves, immune cells, microneuromas, and conjunctival blood vessels. These clinical parameters cannot be measured by conventional clinical assessment alone. The combination of these imaging modalities with clinical feedback provides unparalleled quantification information of the dynamic properties and functional parameters of different ocular surface tissues. Moreover, image-based biomarkers provide objective, specific, and non / marginal contact diagnosis, which is faster and less unpleasant to the patient’s eye than the clinical assessment techniques. The aim of this PhD thesis was to introduced deep learning-based novel computational methods to segment and quantify meibomian glands (both upper and lower eyelids), corneal nerves, and dendritic cells. The developed methods used raw images, directly export from the clinical devices without any image pre-processing to generate segmentation masks. Afterward, it provides fully automatic morphometric quantification parameters for more reliable disease diagnosis. Noteworthily, the developed methods provide complete segmentation and quantification information for faster disease characterization. Thus, the developed methods are the first methods (especially for meibomian gland and dendritic cells) to provide complete morphometric analysis. Taken together, we have developed deep learning based automatic system to segment and quantify different ocular surface tissues related to DED namely, meibomian gland, corneal nerves, and dendritic cells to provide reliable and faster disease characterization. The developed system overcomes the current limitations of subjective image analysis and enables precise, accurate, reliable, and reproducible ocular surface tissue analysis. These systems have the potential to make an impact clinically and in the research environment by specifying faster disease diagnosis, facilitating new drug development, and standardizing clinical trials. Moreover, it will allow both researcher and clinicians to analyze meibomian glands, corneal nerves, and dendritic cells more reliably while reducing the time needed to analyze patient images significantly. Finally, the methods developed in this research significantly increase the efficiency of evaluating clinical images, thereby supporting and potentially improving diagnosis and treatment of ocular surface disease

Developing a non-pharmacological intervention model to improve function and participation in people with primary Sjögren's syndrome

PhD ThesisBackground: Primary Sjögren’s syndrome (PSS) is an autoimmune disease which primarily targets secretory glands causing sicca/dryness symptoms. Patients with PSS also experience a range of other symptoms including fatigue, pain, sleep disturbances, low mood and anxiety. These symptoms impact on activities of daily living, participation and quality of life. PSS has been an under researched disease, and as a consequence many needs of patients remain unmet within clinical settings. Aim: To design a non-pharmacological intervention strategy for people with PSS focussing on patient-relevant targets in order to improve daily function and participation. Methods: In this project, I use a mixed methods approach. I conducted a systematic review of published interventions of non-pharmacological interventions for PSS. Then concept mapping, a participatory mixed methods approach, was used to identify factors which interfere with performance of daily activity for people with PSS. These results were discussed with a steering group and used as a basis to develop an intervention strategy. I then conducted focus groups with patients and their spouses to discuss the main factors deemed to interfere with activities, ascertain strategies patients use to manage these problems, and to determine the acceptability of potential future interventions to address these factors. Finally a model for the delivery of non-pharmacological interventions to address these factors was developed with patients. Results: The systematic review found there was insufficient published evidence to either support or refute non-pharmacological interventions for PSS. The concept mapping study revealed that in addition to dryness; fatigue, pain and sleep disturbances were priority targets for future interventions. The qualitative focus groups demonstrated that patients currently deploy a range of strategies to self-manage fatigue, sleep and v pain. However, these strategies are not always successful and patients require individualised therapies which target their own priorities and required level of support. Conclusion: The work within this thesis provides a comprehensive understanding of factors which influence daily function and participation in PSS patients. This work presents a stakeholder-informed model for delivering future non-pharmacological interventions to address stakeholder informed priorities. As such, a model has been developed which will ultimately support patients to manage symptoms of fatigue, sleep disturbances and pain, which are perceived by patients, their families and health professionals to impact on performance of daily activities and participation.Arthritis Research UK for awarding me a Nurse and Allied Health Professional Training Fellowship and to the United Kingdom Occupational Therapy Research Foundation for awarding me with a Research Career Development Award. This funding has meant that this research could take place

Technology 2002: the Third National Technology Transfer Conference and Exposition, Volume 1

The proceedings from the conference are presented. The topics covered include the following: computer technology, advanced manufacturing, materials science, biotechnology, and electronics

Oxidative Stress and Inflammation

In the biochemical reactions that take place within all living beings, species called free radicals are generated. Denham Harman, in his study on the origin and evolution of life (Harman, 2001), proposes that these species are amongst the causes of the origin of life on our planet. Oxygen is a molecule that provides the primary source of energy in aerobic organisms and therefore is key to the development and evolution of life. On the one hand, it gives rise to life; on the other, due to its ability to form different free radicals, it is capable of damaging essential structures for development. To combat these radicals, our biological systems have developed antioxidant defenses. However, when the balance between free radicals and antioxidant defenses is broken in favor of the former, a phenomenon called oxidative stress occurs, which ends up damaging molecules such as DNA, proteins, carbohydrates, and lipids (Sies, 1983) (Halliwell and Gutteridge, 1985). This phenomenon is implicated both in the development of diseases and in their progression. In addition, inflammation phenomena are also involved in most pathologies, which, although they are essential for tissue repair and immunity, turn against our bodies when they become excessively active. For these reasons, in this special edition we showcase an extensive knowledge of the effects of oxidative stress and inflammation both in diseases such as aging, or for its role in health

T cells in atopic eye disease

Background: Chronic allergic eye diseases comprise a clinically heterogeneous group of disorders, including atopic blepharoconjunctivitis (ABC), giant papillary conjunctivitis (GPC), vernal keratoconjunctivitis and atopic keratoconjunctivitis (AKC). The latter two are the most serious conditions by far, since both can be accompanied by corneal inflammation and represent potentially blinding disorders. Treatment with conventional mast cell stabilisers is often unsatisfactory and therapy therefore frequently relies on topical corticosteroids. Although a cell mediated immune response is thought to be involved in these diseases, very little is known about the cellular interactions leading to the immunopathology. T cells have been subdivided on the basis of their lymphokine production profile in the murine system. Recent evidence suggests the existence of such T cell subsets in the human system. T lymphocytes producing Interleukin (IL-) 4 and IL- 5 but no or little IL-2 and IFNy are thought to play an important regulatory role in the immunopathology of other chronic allergic conditions, such as asthma, atopic dermatitis and eczema. Aim: This study was undertaken to investigate the general cellular infiltrate in clinically distinct chronic allergic eye diseases and in particular, to study the distribution of T cell infiltrates and their activation status in order to establish their possible involvement in the regulation of immune processes in chronic allergic eye disease. Methods: Phenotypic differences and similarities of leukocytes infiltrating the different groups of chronic allergic eye disease were investigated employing immunohistochemical staining techniques. Furthermore, the production of lymphokines by T cells was analyzed utilising in situ hybridisation histochemical techniques. The in situ analysis of lymphokine mRNA expression by these T cells was carried out using 35S-labelled riboprobes for IL-2, IL-3, IL-4 and IL-5. Results: Immunohistochemistry revealed a highly significant increase in the number of CD4 + memory (CD45-RO +) T cells in tarsal conjunctival biopsies obtained from patients with VKC and GPC (p<0.001) and a significant increase in tarsal biopsies obtained from patients with AKC (p<0.01). T cells were activated, expressing HLA-DR on their surface. In addition, macrophages and Langerhans cells were upregulated significantly in the conjunctiva of patients with VKC and GPC indicating their possible role in the presentation of antigen to T cells. In situ hybridisation histochemistry revealed a significantly greater number of biopsies from patients with VKC and GPC with signal for IL-3, IL-4 IL-5 and IL-4 mRNA respectively in T cell rich areas of tarsal conjunctiva than normal controls. Although lymphokine mRNA expression was not greater in AKC than normal conjunctiva, several tarsal biopsies from patients with AKC showed mRNA expression for all lymphokines studied. Conclusions: The prevalence of large numbers of CD4+ memory T cells in VKC, GPC and AKC suggested their active involvement in the regulation of the immune response in these chronic allergic eye conditions. Although CD4+ T cells were increased in all allergic patient groups, in situ hybridisation histochemistry revealed differences in lymphokine mRNA expression by T cells infiltrating AKC and VKC. T cells infiltrating VKC bore similarities to murine Th2, while T cells present in AKC revealed a broader spectrum of lymphokine mRNA expression. Therefore, it was put forward that patients with AKC and ABC may have contained T cell populations with a deregulated lymphokine production that led to an overexpression of IL-4 and IL-5 mRNA, while T cells present in VKC and GPC represented possibly normal, late memory T cells producing lymphokines similar to murine Th2

Defense Technical Information Center thesaurus

This DTIC Thesaurus provides a basic multidisciplinary subject term vocabulary used by DTIC to index and retrieve scientific and technical information from its various data bases and to aid DTIC`s users in their information storage and retrieval operations. It includes an alphabetical posting term display, a hierarchy display, and a Keywork Out of Context (KWOC) display

Advances in Ophthalmology

This book focuses on the different aspects of ophthalmology - the medical science of diagnosis and treatment of eye disorders. Ophthalmology is divided into various clinical subspecialties, such as cornea, cataract, glaucoma, uveitis, retina, neuro-ophthalmology, pediatric ophthalmology, oncology, pathology, and oculoplastics. This book incorporates new developments as well as future perspectives in ophthalmology and is a balanced product between covering a wide range of diseases and expedited publication. It is intended to be the appetizer for other books to follow. Ophthalmologists, researchers, specialists, trainees, and general practitioners with an interest in ophthalmology will find this book interesting and useful

Advances in Lipidomics: Biomedicine, Nutrients and Methodology

This book contains 12 articles covering biomedicine, nutrition, and the methodology of lipidomics . These works were first published by MDPI in a Special Issue of Metabolites. Phospholipids, sphingolipids, glyosylinositolphosphoceramides, cholesteryl esters, acyl-carnitines, and oxylipins are within the lipid classes accounted for studies regarding liver disease, Wilson disease, kidney disease, cardiovascular disease, adipogenesis, and the role lipids play in cancer and virus infection. High-throughput lipid extraction and guidelines for lipid annotation are addressed in several papers. This book is expected to provide a comprehensive view of the diverse areas where lipidomics looms largest