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1

Stern, Carla M. "Process efficiency of diagnostic practices in pathology." Thesis, Massachusetts Institute of Technology, 2006. http://hdl.handle.net/1721.1/37229.

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Thesis (M.B.A.)--Massachusetts Institute of Technology, Sloan School of Management, 2006.<br>Includes bibliographical references (leaves 33).<br>The competitive landscape of the health care sector is changing. Private for-profit, private not-for-profit, and public medical care entities along the value chain are increasingly expanding the scope of their business endeavors. This thesis will discuss the evolution of medical services and the metrics used to measure the quality of those services, with particular attention to specialist diagnostic service players in dermatopathology. Hospitals are increasingly competing with private laboratories on the services side, while competing with biotechnology and pharmaceutical companies on the research and development (R&D) side. It is important to understand the factors that contribute to this increasingly complex market for medically related services. This paper includes a review of the empirical literature on metrics to assess quality of care both on a hospital and specialty practice level, a case discussion of a specific dermatopathology practice, and a discussion of the findings from interviews and field research. While it is important to assess the process efficiency of a firm's operations in order to explore the levers for improvement, it is equally important to make sure that the levers used align well with the underlying strategy of the firm.<br>by Carla M. Stern.<br>M.B.A.
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2

Popeliuk, N. O. "Diagnostic accuracy with the pyloroduodenal pathology in children." Thesis, БДМУ, 2020. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/17710.

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3

Deurloo, Eline E. "Correlation of diagnostic breast imaging data and pathology application to diagnosis and treatment /." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2005. http://dare.uva.nl/document/78340.

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4

Maddison, John. "Digital image processing for prognostic and diagnostic clinical pathology." Thesis, University of Huddersfield, 2005. http://eprints.hud.ac.uk/id/eprint/22322/.

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When digital imaging and image processing methods are applied to clinical diagnostic and prognostic needs, the methods can be seen to increase human understanding and provide objective measurements. Most current clinical applications are limited to providing subjective information to healthcare professionals rather than providing objective measures. This Thesis provides detail of methods and systems that have been developed both for objective and subjective microscopy applications. A system framework is presented that provides a base for the development of microscopy imaging systems. This practical framework is based on currently available hardware and developed with standard software development tools. Image processing methods are applied to counter optical limitations of the bright field microscope, automating the system and allowing for unsupervised image capture and analysis. Current literature provides evidence that 3D visualisation has provided increased insight and application in many clinical areas. There have been recent advancements in the use of 3D visualisation for the study of soft tissue structures, but its clinical application within histology remains limited. Methods and applications have been researched and further developed which allow for the 3D reconstruction and visualisation of soft tissue structures using microtomed serial histological sections specimens. A system has been developed suitable for this need is presented giving considerations to image capture, data registration and 3D visualisation, requirements. The developed system has been used to explore and increase 3D insight on clinical samples. The area of automated objective image quantification of microscope slides presents the allure of providing objective methods replacing existing objective and subjective methods, increasing accuracy and rsducinq manual burden. One such existing objective test is DNA Image Ploidy which seeks to characterise cancer by the measurement of DNA content within individual cell nuclei, an accepted but manually burdensome method. The main novelty of the work completed lies in the development of an automated system for DNA Image Ploidy measurement, combining methods for automatic specimen focus, segmentation, parametric extraction and the implementation of an automated cell type classification system. A consideration for any clinical image processing system is the correct sampling of the tissue under study. VVhile the image capture requirements for both objective systems and subjective systems are similar there is also an important link between the 3D structures of the tissue. 3D understanding can aid in decisions regarding the sampling criteria of objective tests for as although many tests are completed in the 2D realm the clinical samples are 3D objects. Cancers such as Prostate and Breast cancer are known to be multi-focal, with areas of seeming physically, independent areas of disease within a single site. It is not possible to understand the true 3D nature of the samples using 2D micro-tomed sections in isolation from each other. The 3D systems described in this report provide a platform of the exploration of the true multi focal nature of disease soft tissue structures allowing for the sampling criteria of objective tests such as DNA Image Ploidy to be correctly set. For the Automated DNA Image Ploidy and the 3D reconstruction and visualisation systems, clinical review has been completed to test the increased insights provided. Datasets which have been reconstructed from microtomed serial sections and visualised with the developed 3D system area presented. For the automated DNA Image Ploidy system, the developed system is compared with the existing manual method to qualify the quality of data capture, operational speed and correctness of nuclei classification. Conclusions are presented for the work that has been completed and discussion given as to future areas of research that could be undertaken, extending the areas of study, increasing both clinical insight and practical application.
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Akin, Faith W. "Diagnostic Procedures for Vestibular Assessment." Digital Commons @ East Tennessee State University, 2001. https://dc.etsu.edu/etsu-works/2456.

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6

Colling, Richard T. "The diagnostic molecular pathology of colorectal carcinoma using automated PCR." Thesis, University College London (University of London), 2017. http://discovery.ucl.ac.uk/1542413/.

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BACKGROUND: Diagnostic molecular testing in colorectal cancer (CRC) offers a number of benefits including predicting prognosis, directing targeted therapies and screening for hereditary cancer syndromes. Molecular testing however is expensive, requires specialist facilities and staff and is time consuming, limiting its widespread availability. The Idylla System is an automated testing platform that could overcome these issues. AIMS: To appraise the suitability of the Idylla System for use in clinical practice by evaluating the system’s accuracy and financial impact. HYPOTHESIS: The Idylla System has high accuracy for detecting mutations in BRAF, KRAS and NRAS genes in CRC resection tissue and is a cost-effective alternative to current testing platforms. METHODS: Ethical approval was granted by Oxfordshire Research and Ethics Committee A (reference: 04/Q1604/21). Diagnostic accuracy was determined for the Idylla System in detecting BRAF and KRAS mutations with a comparison against conventional polymerase chain reaction (PCR). Further validations were also performed for BRAF, KRAS and NRAS mutation testing against NGS and IHC methods. An audit of the molecular diagnostics workload was carried out and a cost-analysis performed. RESULTS: The Idylla system had a sensitivity of 100.0% (95% CI: 88.3% to 100.0%) and a specificity of up to 100.0% (95% CI: 94.7% to 100.0%) for detecting BRAF mutations and a sensitivity of 100.0% (95% CI: 79.6% to 100.0%) and a specificity of up to 92.9% (95% CI: 68.5% to 98.7%) for detecting KRAS Mutations. There was 100% concordance for NRAS testing. A cost-analysis estimated that the Idylla System could save from around £12,000 to anywhere up to £40,000 per year in some centres. CONCLUSIONS: The results support the hypothesis that the Idylla System is an accurate system for detecting relevant mutations in CRC and demonstrate the system to be cost-effective. The Idylla system is therefore suitable for use in routine clinical practice.
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Rapulana, Antony Morwamoche. "Dried spot cards to analyse biologic fluids for diagnostic investigation of patients." Master's thesis, University of Cape Town, 2018. http://hdl.handle.net/11427/29858.

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Background: Collection of biologic fluid for laboratory analysis requires relatively large samples, often with additives, and transport in fragile tubes. The analytes or matrices may be unstable so testing needs to be carried out quickly. Collection of these biologic fluids and drying them on filter paper can lower the cost of transporting the sample to the laboratory, avoid instability of the matrix, and degradation of the analytes. Aim: The aim of this project was to develop an inexpensive, convenient, comprehensive and reproducible patient sample collection system which ensures integrity and ease of transport of small-scale samples at room temperature, as well as ensuring convenient long-term storage for subsequent analysis. Methods: Samples (blood, buffy coat, serum, plasma and urine) were collected into various tubes and spotted onto filter paper cards. Concentrations of total cholesterol, triglyceride, phospholipids, glucose, lactate, and protein were measured in the original sample and dried plasma spots (DPS) and the concentration of creatinine was measured in urine and dried urine spots (DUS). Determination of oxidation of lipids by measurement of conjugated dienes (CD) and thiobarbituric acid reactive substances (TBARS) on dried serum spots (DSS) was carried out. Determination of salicylate on serum and dried serum spots and cyanide on whole blood and dried blood spots was carried out. Values obtained from original samples and dried spots were compared. In addition, DNA extracted from a dried buffy coat spot (DBCS) from a familial hypercholesterolemia patient was analysed after spotting. Results: The total cholesterol, triglyceride, phospholipid, glucose, lactate and protein concentration values of 14 samples were compared in whole plasma and DPS stored at different temperatures. These were highly correlated after 1 week and 3 months of collection and storage. Plasma cholesterol, glucose and lactate concentration values for DPS as well as urinary creatinine for DUS at 1 week were not significantly different to that at both 3 and 7 months’ analyses (p>0.05). Plasma triglyceride and phospholipid concentrations were significantly different (p blood vs DBS respectively) for cyanide. Salicylate in DSS and cyanide in DBS were not significantly different to the original samples (paired t-test, p>0.05). Conclusion: Dried filter spots may be used to transport and store biologic fluid samples for analyses of a number of water-soluble and water-insoluble analytes. To protect lipids from being oxidised, the filter paper should be pre-treated with BHT.
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Antel, Katherine Rae. "Lymphoma: Understanding the diagnostic challenges and improving outcomes in a TBand HIV-endemic area." Doctoral thesis, Faculty of Health Sciences, 2021. http://hdl.handle.net/11427/33628.

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Background and aims Diagnosing lymphoma can be challenging: even in the best-resourced settings, lymphoma diagnosis may be delayed owing to the insidious onset of symptoms and/or difficulties in obtaining lymph node biopsy for diagnosis. In TB-endemic countries the diagnostic challenges in lymphoma may be further compounded by symptoms overlapping with those of TB and by resource limitations that may impede obtaining a diagnostic biopsy. New lymphoma diagnostic modalities, including the use of nextgeneration sequencing, are evolving rapidly and informing both prognosis and therapy in the field of lymphoma. These modalities of testing are likely to mean that less tissue is needed for assessment, or even that diagnosis can be made from peripheral blood. In this thesis we identify and describe local barriers in the diagnosis of lymphoma; and describe methods used to decrease the time-to-diagnosis of lymphoma and to subtype the most common lymphoma, diffuse large B-cell lymphoma (DLBCL). Our four main aims have been to: (i) Describe the pathway to a diagnosis of lymphoma in South Africa, with emphasis on the examination of local barriers to diagnosis (including overlapping symptomatology with TB) by retrospectively studying a cohort of patients with lymphoma. (ii) Investigate the diagnostic utility of the newest TB diagnostic test (the Xpert MTB/RIF Ultra); and apply this test in a diagnostic algorithm for lymphadenopathy of unknown aetiology, both on a fine-needle aspirate (FNA) from a lymph node and on tissue obtained by corebiopsy. (iii) Investigate whether a rapid-access lymph node biopsy clinic that used a core-biopsy method for lymph node biopsy was able to reduce the time-to-diagnosis of lymphoma, and to subtype accurately lymphomas for which subtyping is clinically relevant. (iv) Describe the subtype of DLBCL by HIV status using an immunohistochemical algorithm, in order both to describe the pattern of DLBCL by the most current diagnostic classification and to lay the foundations for further genetic work potentially capable of identifying mutations that could be used for genetic testing in DLBCL locally. Methods Four cohorts were analysed: (i) In the first, a group of 163 patients with lymphoma, the time-to-diagnosis and factors causing a delay in diagnosis were analysed. (ii) In the second, 99 patients with lymphadenopathy of unknown cause were recruited and the sensitivity and specificity of the Ultra were analysed using both fine-needle aspirate (FNA) and a core-biopsy technique. (iii) In the third cohort (n = 130), which included the second cohort of n = 99), outcomes from a rapid-access lymph node biopsy clinic – which used the core-biopsy method for the diagnosis of lymphoma – were analysed. (iv) In the fourth cohort (n = 182), the tissue of patients with DLBCL was analysed based on further immunohistochemical stains using the Hans algorithm in order to determine the molecular subtypes of DLBCL and determine their effect on prognosis. Results (i) In the first cohort ((n = 163), 29% HIV-infected), which was studied retrospectively, it took a median of 7 weeks for the diagnosis of lymphoma to be made from the time the patient sought medical attention. The longest time delay was in the healthcare practitioner interval (time from first healthcare visit to diagnostic biopsy). On multivariable logistic regression analysis, diagnostic delay > 6 weeks was associated with late-stage disease at presentation (odds ratio (OR) 2.3, 95% confidence interval (CI) 1.1–5.2) and a diagnosis of Hodgkin lymphoma (OR 3.0, 95% CI 1.1–8.0). HIV status was not associated with diagnostic delay (OR 0.9, 95% CI 0.3–2.2). The median time to diagnosis for patients on TB treatment was a month longer than for patients not on TB treatment. However, this was not statistically significant owing likely to a small sample size (n = 16, p = 0.28). (ii) In the second cohort, the diagnostic utility of the Ultra on lymph node aspirate and tissue were prospectively evaluated. The Ultra was found to be a sensitive and specific test for diagnosing TB of the lymph node. When compared with culture, the Ultra on aspirate had a sensitivity of 78% (40–97; 7/9) and on tissue 90% (55–100; 9/10). When using a composite reference score that combined both ‘definite TB' (culture positive) and ‘probable TB' (histological and clinical criteria), the Ultra was superior to currently used methods of diagnosing TB of the lymph node, including the detection of AFBs from an aspirate or on tissue biopsy or tissue culture (which had sensitivities of 26%, 33% and 39% respectively). The detection of granulomas on histology had high sensitivity (83%) but the lowest specificity. (iii) In the third cohort, which was studied prospectively, we obtained two important outcomes. Firstly, we showed that a rapid-access lymph node biopsy clinic was able to decrease the time-to-diagnosis of lymphoma when compared with that of cohort one (the historical cohort) to a diagnostic interval of 13.5 days compared with 48 days (p = 0.002). Secondly, the core-biopsy was able to detect lymphoma with a high rate of accuracy. The first-attempt core-biopsy was able to diagnose lymphoma in 84% of cases, and provided sufficient tissue to subtype lymphoma in a high proportion of the lymphoma cases (27/30, 90%). (iv) In the fourth, retrospectively evaluated cohort of patients with DLBCL (n = 181, 51 HIVpositive), there was a similar distribution of germinal centre (GC) and activated B cell (ABC) subtypes in the HIV-infected and HIV-uninfected groups. In contrast to what is reported in HIV-negative DLBCL literature, there were no statistically significant differences in overall survival by DLBCL subtype. Moreover, no significant difference in 5-year overall survival was demonstrated between the GCB and ABC subtypes (HR 1.2, 95% CI 0.8–1.9). Patients with HIV infection with a CD4 count of < 150 CD4 cells/mm3 had significantly poorer survival than those with no HIV infection (HR 2.4, 95% CI 1.3–4.1). Conclusions Making a diagnosis of lymphoma in South Africa is challenging. Two of the greatest challenges are overlapping symptomatology with TB and obtaining an adequate lymph node sample. The Ultra test on lymph node tissue is rapid, sensitive and specific; and can be performed on both FNA and tissue obtained through core-biopsy. Making an accurate diagnosis of TB is of critical importance, as TB is the most common cause for enlarged lymph nodes in TB-endemic areas. A reliable TB test on lymph node tissue will enable both an accurate TB diagnosis and the identification of patients who are negative for TB. The latter will require further investigation with a lymph node biopsy (via core needle or excision). As diagnostic testing and methods evolve in the direction of next-generation platforms, it is important to understand the tumour biology in our local setting, and in HIV-lymphoma, in order to be able to apply these new methods. This thesis describes the subtypes and outcomes seen in HIV DLBCL – knowledge that will be important in developing genetic next-generation sequencing methods that are specific to the type of lymphoma to be found in our context (and which may include genetic mutations induced by the Epstein–Barr virus). A clear diagnostic algorithm for the investigation of lymphadenopathy is presented, pulling together the four aims presented at the start of this section. Considering the prevalence of TB in South Africa, the goal is, in the first instance, to diagnose or exclude TB adenitis. In patients who test negative for TB, the goal then becomes to proceed with a diagnostic biopsy and, from our findings, to support the use of core-biopsy. This method, we have demonstrated, is able to provide sufficient tissue for the diagnosis and subtyping of lymphoma.
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9

Hand, N. M. "A study of the use of hydrophilic resins in diagnostic histopathology." Thesis, University of Nottingham, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.381432.

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10

Nagala, Sidhartha. "Correlating thyroid tumour pathology with magnetic resonance biomarkers to improve pre-operative diagnosis." Thesis, University of Cambridge, 2014. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708232.

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11

Mudariki, Temba. "Diagnostic neuropathology of brain tumours using biophotonics and spectrometry." Thesis, University of Central Lancashire, 2016. http://clok.uclan.ac.uk/16665/.

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Classification of tumours such as gliomas, which are on a continuous spectrum of histology and malignancy into distinct categories is still a challenge using histopathology. There has been significant advances in the techniques used to fight cancer in the past two decades. A number of studies have looked at different approaches to improve the accuracy in diagnosis using histopathology. This study evaluated a number of techniques to compliment histopathology. One study looked at vibrational spectroscopy, Raman and attenuated total reflection-fourier transform infrared (ATR-FTIR) looking at brain tumour cell lines. This study investigated the potential application of vibrational spectroscopy in the segregation of different types of brain tumours using two tumour cell lines, U87MG, 1321N1 and a control, SVGP12. Another study looked at two approaches, elemental profiling of both tissue and serum using inductively coupled plasma-mass spectrometry. Trace elements increase or deficiency has been linked to cancer development and progression. The final study looked at the diagnostic application of Raman spectroscopy to distinguish between gliomas, meningiomas, medulloblastoma and several other brain tumours from histological normal brain tissue from brain tumour patients used as controls. The three cell lines U87MG, SVGP12 and 1321N1 were cultured and grown on calcium fluoride slides in triplicates. Spectra from each cell line was taken using both Raman and ATR-FTIR. The spectra was then analysed using multivariate statistics. In the elemental profiling study serum and tissue samples from 55 patients with brain tumours were collected and analysed using ICP-MS. The elemental data was then evaluated using multivariate statistics to investigate significant differences. In the analysis of human brain tumours tissue blocks of both tumour and histological normal brain that were formalin fixed and paraffin embedded (FFPE) were processed and mounted on low-E slides, dewaxed using Xylene, washed with alcohol and water before storage at room temperature until analysis. Raman and ATR-FTIR were able to separate U87MG, SVGP12 and 1321N1 with very high classification accuracy. All the brain tumour groups investigated showed a deficiency of Mg, Fe, Cu, and Zn concentrations against reported levels from healthy individuals in the literature. Raman spectroscopy coupled with multivariate statistics was able to distinguish between normal brain tissue and normal brain tumour tissue used as controls. Classification of gliomas based on the degree of malignancy was also apparent with very high classification accuracy. Spectral panels were developed that can be used as biomarkers in the diagnosis of brain tumours. Raman and Infrared spectroscopy are types of vibrational spectroscopy which have the potential to be used as diagnostic tools in neuropathology. They provide an intrinsic molecular fingerprint of the sample based on the interaction of light. The panels can accurately identify and classify specific brain tumours alleviating the need to use complex statistical models. Raman and ATR-FTIR were able to elucidate chemical information from the samples which was used to differentiate the three cell lines with very high classification accuracy. Diagnosis of a brain tumour is not always a straight forward process and the current techniques used lack the desired level of precision in diagnosis and cytoreductive surgery.
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Ssekitoleko, Robert Tamale. "Design and fabrication of micro-scale high frequency ultrasonic diagnostic devices for in-vivo pathology." Thesis, University of Strathclyde, 2014. http://oleg.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=24299.

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Transducer arrays operating above 15 MHz enable real time high resolution imaging of tissue, capable of resolving features below 200μm. Clinical applications such as oncology and gastroenterology could significantly benefit from the improved resolution for high frequency ultrasound (HFUS) characterization of tissues. However, this is presently challenging due to the limited penetration depth of HFUS and limited access. Since the device dimensions scale with imaging wavelength, it becomes feasible to integrate HFUS arrays with interventional tools such as biopsy needles. Although there are many design and fabrication challenges associated with incorporating transducers with interventional tools such as biopsy needles, it creates opportunities for timely and accurate characterisation of tissue, leading to in-vivo pathology. This study reports progress in the development of fabrication processes for miniature linear arrays suitable for integration with biopsy needles. While patterning high frequency transducer arrays based on piezocomposites has been shown to be feasible, there remain many challenges to miniaturize the interconnect and cabling of an ultrasound probe suitable for in vivo pathology. Novel packaging techniques for integrating an ultrasound array into a needle were developed. Wafer scale fabrication was adopted to reduce the overall cost of fabrication. Microfabrication and precision micromachining processes were developed to overcome the technical challenges in fabricating miniature arrays operating up to 25 MHz. Array elements are defined by precision dicing and the necessary external flex circuit cabling was fed through the needle. A flexible printed circuit is connected to back surface electrodes using low-temperature bonding methods. A flex circuit connected to the 1-3 piezocomposite was patterned with 60 μm pitch to define array elements suitable for a 25 MHz linear array. The polyimide flexible printed circuit, with fine pitch traces, was twisted into a helical structure so that it can fit within the core of the biopsy needle and permit large numbers of elements and electrode traces. The spiral-helical flexi-circuit design was developed as a way to fit multiple conductive tracks into a needle. The definition of fine-pitch conductive tracks on polyimide polymer was achieved using dry-film photoresist and the application of a megasonic transducer to provide agitation and small bubbles for copper etching. Investigation and evaluation of low temperature bonding methods was undertaken. This overcomes the problem of using high temperature methods on the temperature sensitive single crystal materials. Bonding techniques such as ultrasonic bonding and magnetically aligned anisotropic UV curable epoxy were investigated. A Resolution integral was applied to simulated beam plots as a way of evaluating transducers at a design stage. This considers the ultrasound beams and a measure of the beam at -6 dB is taken as the lateral resolution. This is measured over the depth of field. A transducer with a higher resolution integral would have a narrow beam over a long distance The process was validated with a single element transducers made from fine-scale single crystal composites involving PMN-PT and Manganese doped Lead Indium Niobate-Lead Magnesium NiobateLead Titanate (Mn-PIN-PMN-PT). These were fabricated using the conventional dice and fill method, and incorporated into needles and tested. These composites had pitches as small as 50 μm with kerf of 18 μm. Images were generated using these transducers. Arrays operating at 5 MHz and 15 MHz were fabricated. The fabrication process development and testing demonstrated the feasibility of a linear array integrated into a biopsy needle. The extension of the fabrication processes to higher frequency arrays.
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Wang, Xiangxue. "A PROGNOSTIC AND PREDICTIVE COMPUTATIONAL PATHOLOGY BASED COMPANION DIAGNOSTIC APPROACH: PRECISION MEDICINE FOR LUNG CANCER." Case Western Reserve University School of Graduate Studies / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=case1574125440501667.

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Haddad, Jane Wurster 1965. "Evaluation of diagnostic clues in histopathology through image processing techniques." Thesis, The University of Arizona, 1990. http://hdl.handle.net/10150/277296.

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The primary method for the diagnostic interpretation of histopathologic sections is visual analysis. However, in a small, but significant percentage of cases, histopathologists do not come to a consensus. Therefore, due to the importance of early and accurate detection of tissue changes indicative of pathology, quantitative image analysis techniques have been applied to this problem. The accurate segmentation of image structures such as cells and glands in histopathological sections, as with all "natural scenes", proves challenging. This has led to the development of an additional segmentation technique, the heuristic gradient search. Following the successful segmentation and labeling of scene objects, algorithms evaluating diagnostic clues as to the shape, size and distribution of image components were developed in order to form an overall diagnosis. A description of these diagnostic clues and the image processing techniques residing in the computer vision system used to evaluate them are presented.
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Smurzynski, Jacek. "Frequency Modulated Distortion-product Otoacoustic Emission (FMDPOAE) Tests Aimed for Improving Diagnostic Performance." Digital Commons @ East Tennessee State University, 2016. https://dc.etsu.edu/etsu-works/2220.

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Rezgui, Chaabouni Hajer. "Diagnostic d'ouvrages en maçonnés : Méthodes Soniques Impact-Echo." Thesis, Limoges, 2020. http://www.theses.fr/2020LIMO0060.

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Le patrimoine d’ouvrage d’art Européen et en particulier français est vieillissant. Pour pouvoir le conserver, il est nécessaire d’établir un ‘état de santé’ de ces ouvrages en les auscultant. Afin de ne pas les dégrader lors de l’auscultation des méthodes de contrôle non destructifs (CND) doivent être utilisées. Nous nous sommes intéressés en particulier, à une méthode connue sous le nom d’Impact-Echo. La pathologie qui a retenu notre attention concerne les vides ou les défauts pouvant être situés dans le remplissage des ponts en maçonnerie, au-delà des voûtes ou des murs de têtes. Afin de tirer le meilleur profit de la méthode d’auscultation, une étude numérique permettant de simuler un Essai Impact-Echo sur une structure sous forme de plaque bicouche contenant un défaut est développée. Devant la difficulté d’interprétation des résultats issus de cette simulation, un plan d’expériences factoriel numériques est introduit. Pour ce plan d’expériences quatre facteurs sont retenus. Deux facteurs liés la géométrie de la structure e1 et d, un facteur lié aux matériaux composant la structures R et un facteur purement numérique . D’autres variables de sortie, autre que la lecture de la position du pic, sont introduites. A l’issue de ce plan d’expériences, nous avons pu dégager des relations, qui ont permis de lier les facteurs d’entrée aux différentes variables de sortie. Ces relations ont été testées, dans un premier temps, sur les données ayant servi à les établir. Une compagne expérimentale a été introduite afin de valider la simulation numérique. Pour cette validation, nous avons tenté d’exploiter les essais de la compagne expérimentale à l’aide des différentes relations obtenues du plan d’expériences numériques<br>The heritage of European and particularly French infrastructure is aging. To be able to preserve it, it is necessary to establish a "state of health" of these works by auscultation. In order not to degrade them during the auscultation, non-destructive testing (NDT) methods must be used. We were particularly interested in a method known as the Impact-Echo method. The pathology that caught our attention concerns voids or defects that may be located in the filling of masonry bridges, beyond the vaults or the head walls. In order to make the most of the auscultation method, a numerical study to simulate an Impact-Echo test on a bilayer structure containing a defect is developed. Faced with the difficulty of interpreting the results from this simulation, a numerical factorial design of experiments is introduced. For this experimental design four factors are retained. Two factors linked to the geometry of the structure e1 and d, a factor linked to the materials composing the structures R and a purely numerical factor . Other output variables, other than reading the peak position, are introduced. At the end of this experimental design, we were able to identify relations, which made it possible to link the input factors to the different output variables. These relations were first tested on the data used to establish them. An experimental campaign was introduced in order to validate the numerical simulation. For this validation, we tried to exploit the trials of the experimental companion using the different relations obtained from the numerical factorial design of the experiment
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Walters, Jaco. "Diagnostic accuracy of maxillary periapical pathology perforating the sinus floor: a comparison of pantomograph and CBCT images." University of Western Cape, 2020. http://hdl.handle.net/11394/7349.

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>Magister Scientiae - MSc<br>Periapical lesions are fairly common pathology associated with the apex of a non-vital tooth. Some chronic lesions develop without an acute phase with no recollection of previous symptoms. It is known that maxillary odontogenic infections can breach the sinus floor with succeeding complications. Pantomography, a widespread conventional radiographic technique, provides a generalized view of the maxillofacial region. Advanced modalities like CBCT may facilitate in navigating complex anatomy, which would otherwise be obscured.
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Setyo, Laura Christina. "Immunohistochemical study of urothelial carcinoma of the urinary bladder: diagnostic and therapeutic implications." Thesis, The University of Sydney, 2021. https://hdl.handle.net/2123/26760.

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Invasive urothelial carcinoma (UC) is the most common form of urinary bladder cancer and most dogs ultimately die of the disease. It is derived from urothelium, a unique, highly specialised epithelium which lines the lower urinary tract and functions as a physical barrier as well as a sensory structure. Canine UC is believed to be an appropriate animal model because canine UC shares many characteristics with human UC. A substantive comparative study on tumorigenic molecules expressed by canine and human UC is anticipated as an important development toward understanding the mechanism. Tyrosine kinases are proteins that phosphorylate other proteins on tyrosine residues. Evidence suggests that in both human and veterinary patients, tyrosine kinases are often abnormally activated in malignant tumours. Examples of receptor tyrosine kinases include Kit and VEGFR2, all of which are known to be dysregulated forms of cancer. Toceranib phosphate (Palladia®; Pfizer Animal Health, Madison, NJ, USA) is an oral oxindole receptor tyrosine kinase inhibitor that blocks the activity of VEGFR2, PDGFRα/β, FLT-3, KIT and CSFR1. The aims of this study were to extend the knowledge about the immunohistochemical factors involved in urothelial carcinogenesis and identify risk factors for development of UC.
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Erickson, Heidi S. "Characterization of Taura syndrome virus (TSV) isolates from Penaeid shrimp: Pathology, virulence, structural protein analysis and genetic diversity, and, Development of the aquaculture pathology diagnostic laboratory database." Diss., The University of Arizona, 2002. http://hdl.handle.net/10150/280124.

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In the research reported here, the pathology, virulence, and strain differences of Taura syndrome virus (TSV) was studied. Initial studies on TSV pathogenesis compared the survival of juveniles of a highly Taura syndrome (TS) susceptible line of Penaeus vannamei, a line of TS resistant P. vannamei, and an innately TS resistant P. stylirostris line following TSV challenge by feeding (per os) or injection methods, in the absence of horizontal transmission via cannibalism and/or absorption from the water. Per os_TSV challenge resulted in I00% survival in P. stylirostris, but challenge by per os exposure produced significant mortality commencing on about the same post-exposure day in both SPF and SPR P. vannamei (P < 0.001), suggesting that P. stylirostris is significantly (P < 0.001) more resistant toper os TSV infection and presentation of TS disease than either SPF or SPR P. vannamei. The potential roles of the cuticular lining of the stomach and hindgut and unlined portions of the gut in TSV resistance in penaeid shrimp are discussed as factors where an innate resistance mechanism was postulated to explain the observed differences between the different species and populations of shrimp in TSV susceptibility. To investigate apparent TSV strain differences, three geographic and year isolates of TSV from naturally occurring TS epizootics of cultured penaeid shrimp were obtained from Mexico (SIN98TSV and MX99TSV from P. vannamei and SON2KTSV from P. stylirostris) and one TSV isolate from Belize, Central America (BLZ02TSV from P. vannamei) were analyzed and compared to the reference TSV isolate (HI94TSV) by selected TSV diagnostic and genetic analysis methods. The results show that screening of penaeid shrimp broodstock and postlarvae by MAb I Al testing will not detect all TSV isolates, possibly leading to false negative results, further spread of TSV and re-emergence of TS in regions where it has been eradicated. The putative VP1 antigenic epitope recognized by TSV MAb 1A1 is identified, with SIN98TSV and BLZ02TSV having 70.0% and 80.0% AA homology, respectively, within the 10 AA region. There are three distinct electropherotypes and 'serotypes' of TSV, with electropherotype A (TSV Etype-A) and serotype A (TSV-A) representing those TSV isolates conforming to VP1 properties of the Hawaiian 1994 TSV isolate, electropherotype B (TSV Etype-B) and serotype B (TSV-B) representing those TSV isolates conforming to the VP1 properties of the Sinaloan 1998 TSV isolate, and electropherotype C (TSV Etype-C) and TSV serotype C (TSV-C), representing those TSV isolates conforming to the VP1 properties of the Belize 2002 TSV isolate. In a parallel activity, the University of Arizona (UAZ) Aquaculture Pathology Diagnostic Laboratory (APL) Case Database (DB) and the UAZ Aquaculture Pathology Diagnostic Laboratory Client Address Book Database (AB), relational databases, were created using FileMaker Pro software, are used to keep an up to date and accurate record of all UAZAPL diagnostic and research case and client information and may be searched and sorted to find case data and/or client information of interest.
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Logan, Patrick 1982. "In vivo imaging of liver metastasis using green fluorescent protein labelled human uveal melanoma cells in a mouse model." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=112536.

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Uveal melanoma is the most common primary malignant intraocular tumour in adults and despite advances in treatment of the primary tumour, the 10-year survival rate remains unchanged. The most frequent cause of death for patients of this disease is liver metastases. Removal of the primary tumour before clinical presentation of metastases, however, has no effect on patient outcome.<br>In order to understand the interactions between single malignant cells or sub-clinical metastases and affected organs, we have successfully developed a novel animal model of uveal melanoma. We utilized the unique properties of green fluorescent protein, a skin-flap in vivo imaging technique, and nude mice to accomplish this goal. The precision of green fluorescent protein imaging has allowed us to observe single cells interacting with organ tissues and reveal that these malignant cells are only capable of surviving in the liver.
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Mina, Ashraf Anis Wahba. "Improving and Implementing Diagnostic Tools in Pathology with a Focus on Haemostasis and Association with Select Endocrine Disorders." Thesis, The University of Sydney, 2013. http://hdl.handle.net/2123/10599.

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The literature and evidence base associating haemostatic dysfunction associated with some of endocrine disorders as major risk factors and causes of human morbidity and mortality was reviewed and published. A detailed protocol to define and develop instrument selection and evaluation and implementation in pathology and research, also its impact on method development and objective evaluation was developed and published. A new quality control model using performance goals based on biological variation in External Quality Assurance Schemes was developed and published. A robust and cost effective method for estimating iodine as indicator of thyroid abnormality which can be used to identify patients with thyroid disorders that are prone to risk of bleeding and/or thrombosis was developed and published. A novel functional assay to estimate Von Willbrand factor (VWF)/antigen and collagen binding was developed and published. Evaluation of short activated partial thromboplastin times (APTT), as potential representation of a complex hypercoagulant milieu that could feasibly contribute to thrombotic risk, was assessed and published. Assessment of the relationship between short APTTs, thrombin generation, procoagulant factors [fibrinogen and Factors (V, VIII, IX, XI and XII)], VWF, and procoagulant phospholipid activity was also achieved and published. A study designed to investigate select haemostasis, endocrine and biochemical parameters in women who undergo in-vitro fertilisation, before and after stimulation with follicle stimulating hormone was achieved and submitted for publication.
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GAMBINI, MATTEO. "PATHOLOGY OF ROUND CELL TUMORS AND SARCOMAS: A DIAGNOSTIC AND CLINICALLY-ORIENTED APPROACH, WITH A FOCUS ON BASIC INVESTIGATION." Doctoral thesis, Università degli Studi di Milano, 2021. http://hdl.handle.net/2434/829077.

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Neoplasms represent a constantly increasing threat for companion animals, requiring fast and reliable diagnostic techniques. In this context, cytology is a diagnostic tool widely applied to preliminarly investigate the nature of lesions observed in daily veterinary practice. Nevertheless, considered the limitations of cytology as well as the key role that a cytological diagnosis might cover for the clinical approach to each patient, estimation of the reliability of this technique represents a fundamental step. With this in mind, diagnostic accuracy studies can provide a proof of reliability of cytological results, when the latter are compared to the histopathological gold standard. With these premises, the main aim of the current Thesis was to evaluate the diagnostic accuracy of cytology applied to different round cell tumors and sarcomas currently representing a serious threat for the canine and feline species. Chapter 1 describes a study investigating the diagnostic accuracy of cytology in the evaluation of canine splenic neoplasm. To the best of our knowledge, our work was the first study conjunctively reporting overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of cytology in the diagnosis of these lesions. Diagnostic accuracy indexes identified limitations of negative cytological results in excluding a dog to be truly free from neoplasia; however, high specificity and positive predictive value still highlighted cytology as a valuable tool in the diagnostic approach to splenic neoplasms. In Chapter 2 is described a study investigating interobserver agreement and diagnostic accuracy of cytology in the immunophenotype prediction of feline nodal lymphoma. Our results revealed a low inter-observer agreement and a low diagnostic accuracy in immunophenotype prediction, thus highlighting potential marked differences among laboratories and even among different cytologists within the same laboratory, and consequently the mandatory need of histopathology and immunohistochemistry for a correct interpretation of feline nodal lymphoma immunophenotype. Chapter 3 describes two studies focusing on the application of cytology in the evaluation of nodal metastasis of canine mast cell tumor (MCT). The preliminary investigations described in Section 1 focused on the quantification of mast cells in cytological nodal samples obtained from both non oncological dogs and MCT-bearing dogs, revealing that mast cell (MC) quantification in lymph node (LN) cytological samples obtained from the latter might be useful to determine the nodal metastatic status. Our findings further suggested that neither the sampling technique applied to collect cytological samples nor the quantification method applied to estimate the number of MCs, influence the number of nodal MCs observed. Section 2 describes a study investigating interobserver agreement and diagnostic accuracy of cytology in the evaluation of the metastatic status of lymph nodes obtained from MCT-bearing dogs. Specifically, the study investigated the diagnostic performance of the cytological interpretative system currently available in literature as well as that of 2 amendments of the latter (AM1 and AM1.2 system). Our results revealed that the AM1.2 system, which include MC quantification besides the cytological criteria reported in the previously published cytological interpretative system, could represent a valid alternative to the latter, being characterized by an almost overlapping interrater agreement, and sensibly higher accuracy and sensitivity without substantial changes of the other diagnostic accuracy indexes. Besides studies focusing on the diagnostic accuracy of cytology, the Addendum briefly describes the results of 2 research projects investigating viral oncolysis in a cell culture model of canine histiocytic sarcoma, performed by the Ph.D. candidate during his externship at the University of Veterinary Medicine of Hannover (TiHo Hannover, Germany).
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Smurzynski, Jacek. "Otoacoustic Emissions: The Influence of the Middle-ear Function, SFOAEs, and OAEs as a Diagnostic Predictor for Cochlear Impairment." Digital Commons @ East Tennessee State University, 2012. https://dc.etsu.edu/etsu-works/2160.

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Dorofeev, A. E., S. V. Kovalenko, and Yu F. Marchuk. "Comparison of clinical-diagnostic picture of private forms of gastrointestinal system pathology by bronchial asthma and chronic obstructive pulmonary disease." Thesis, БДМУ, 2011. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/17880.

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25

Chaudry, Qaiser Mahmood. "Improving cancer subtype diagnosis and grading using clinical decision support system based on computer-aided tissue image analysis." Diss., Georgia Institute of Technology, 2013. http://hdl.handle.net/1853/47745.

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This research focuses towards the development of a clinical decision support system (CDSS) based on cellular and tissue image analysis and classification system that improves consistency and facilitates the clinical decision making process. In a typical cancer examination, pathologists make diagnosis by manually reading morphological features in patient biopsy images, in which cancer biomarkers are highlighted by using different staining techniques. This process is subjected to pathologist's training and experience, especially when the same cancer has several subtypes (i.e. benign tumor subtype vs. malignant subtype) and the same cancer tissue biopsy contains heterogeneous morphologies in different locations. The variability in pathologist's manual reading may result in varying cancer diagnosis and treatment. This Ph.D. research aims to reduce the subjectivity and variation existing in traditional histo-pathological reading of patient tissue biopsy slides through Computer-Aided Diagnosis (CAD). Using the CAD, quantitative molecular profiling of cancer biomarkers of stained biopsy images are obtained by extracting and analyzing texture and cellular structure features. In addition, cancer sub-type classification and a semi-automatic grade scoring (i.e. clinical decision making) for improved consistency over a large number of cancer subtype images can be performed. The CAD tools do have their own limitations and in certain cases the clinicians, however, prefer systems which are flexible and take into account their individuality when necessary by providing some control rather than fully automated system. Therefore, to be able to introduce CDSS in health care, we need to understand users' perspectives and preferences on the new information technology. This forms as the basis for this research where we target to present the quantitative information acquired through the image analysis, annotate the images and provide suitable visualization which can facilitate the process of decision making in a clinical setting.
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Chapel, Gwenda-ella. "Modélisation et diagnostic des conceptions d'élèves de niveau seconde sur l'information génétique, lors de l'élaboration d'expérience à l'aide de LabBrook." Phd thesis, Université de Grenoble, 2011. http://tel.archives-ouvertes.fr/tel-00721782.

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Les objectifs de ce travail (la modélisation et le diagnostic) sont réalisés grâce à la création et la mise en place d'une situation d'élaboration d'expérience où les élèves répondent au problème suivant : Comment modifier l'information génétique ? La situation de recueil des productions fait intervenir le site internet LabBook, comprenant plusieurs éditeurs dont COPEX, qui étaye l'activité d'élaboration de protocole expérimental. Cette situation permet de proposer un environnement de travail sur les neuf niveaux biologiques auxquels les élèves peuvent placer l'information génétique : Milieu, Organisme, Organe, Cellule, Noyau, Caryotype, Chromosome, Gène et ADN. Ces niveaux ont été déterminés à partir de l'étude de travaux sur les difficultés des élèves en génétique et d'une analyse épistémologique du savoir. La situation a été proposée à la suite d'une analyse a priori effectuée dans le cadre de la TSD de Brousseau (1998) et du modèle cK¢ de Balacheff (1995). L'analyse des productions d'élèves nous apporte des informations sur le niveau biologique auquel ils souhaitent réaliser leur expérience, sur l'objet biologique du niveau choisi, ainsi que le mode de modification de l'information génétique. Nous retrouvons un plus grand nombre de réponses aux niveaux Chromosome, Gène et ADN. Concernant les objets biologiques, ce sont ceux donnant leur nom aux niveaux qui sont les plus utilisés et la modification principale est un échange, une substitution. Le modèle cK¢ a aussi servi à formaliser les conceptions dégagées des productions des élèves. Nous avons pu modéliser neuf conceptions rassemblant la moitié des élèves et correspondant à la modification de l'information génétique.
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Klein, koerkamp Yanica. "Atteintes amygdaliennes et troubles émotionnels dans la maladie d'Alzheimer : apport de nouvelles pistes pour le diagnostic." Phd thesis, Université de Grenoble, 2013. http://tel.archives-ouvertes.fr/tel-00933331.

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Le diagnostic de la maladie d'" Alzheimer " (MA) repose essentiellement sur des tests neuropsychologiques, démontrant d'importants déficits mnésiques en lien avec l'atrophie de l'hippocampe. Parallèlement à cela, l'existence d'une atteinte précoce de l'amygdale a très récemment été proposée dans une série d'études, suggérant que cette structure pourrait être un marqueur neuro-anatomique de l'entrée dans la maladie. Les études ayant évalué les répercussions émotionnelles de ces atteintes amygdaliennes n'ont néanmoins pas permis d'aboutir à l'identification d'un profil convergent de déficits. L'objectif de cette thèse a donc été de démontrer l'existence d'une atteinte de l'amygdale à un stade précoce de la MA entrainant des modifications des traitements émotionnels. Dans une première étude en neuroimagerie structurelle, nous avons montré des arguments robustes quant à l'existence d'atteintes anatomiques de l'amygdale chez des patients légèrement atteints par la maladie. L'amplitude de cette atrophie s'est avérée être un indicateur particulièrement sensible du niveau général d'atteintes cognitives mesurées chez nos patients. Dans les études suivantes, nous nous sommes intéressés aux répercussions de cette atteinte sur des activités cognitives sous-tendues plus directement par le fonctionnement de cette structure : les traitements émotionnels. Par l'élaboration d'une méta-analyse, nous avons pu identifier un déficit précoce de la reconnaissance des émotions. Nous avons de plus démontré que les troubles cognitifs des patients expliquaient en partie le déficit émotionnel, sans toutefois l'expliquer dans sa totalité. Enfin, une série d'études comportementales et en neuroimagerie fonctionnelle, a permis de confirmer que les atteintes anatomiques s'accompagnaient bien d'un dysfonctionnement de l'amygdale entrainant des déficits émotionnels, en particulier dans les mécanismes à l'origine de l'extraction spontanée de la saillance émotionnelle. L'ensemble de nos données convergent vers l'idée que l'atteinte amygdalienne et les altérations des mécanismes émotionnels seraient une piste prometteuse afin de préciser le diagnostic actuel de la MA.
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28

Traore, Lamine. "Semantic modeling of an histopathology image exploration and analysis tool." Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066621/document.

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La formalisation des données cliniques est réalisée et adoptée dans plusieurs domaines de la santé comme la prévention des erreurs médicales, la standardisation, les guides de bonnes pratiques et de recommandations. Cependant, la communauté n'arrive pas encore à tirer pleinement profit de la valeur de ces données. Le problème majeur reste la difficulté à intégrer ces données et des services sémantiques associés au profit de la qualité de soins. Objectif L'objectif méthodologique de ce travail consiste à formaliser, traiter et intégrer les connaissances d'histopathologie et d'imagerie basées sur des protocoles standardisés, des référentiels et en utilisant les langages du web sémantique. L'objectif applicatif est de valoriser ces connaissances dans une plateforme pour faciliter l'exploration des lames virtuelles (LV), améliorer la collaboration entre pathologistes et fiabiliser les systèmes d'aide à la décision dans le cadre spécifique du diagnostic du cancer du sein. Il est important de préciser que notre but n'est pas de remplacer le clinicien, mais plutôt de l'accompagner et de faciliter ses lourdes tâches quotidiennes : le dernier mot reste aux pathologistes. Approche Nous avons adopté une approche transversale pour la représentation formelle des connaissances d'histopathologie et d'imagerie dans le processus de gradation du cancer. Cette formalisation s'appuie sur les technologies du web sémantique<br>Semantic modelling of a histopathology image exploration and analysis tool. Recently, anatomic pathology (AP) has seen the introduction of several tools such as high-resolution histopathological slide scanners, efficient software viewers for large-scale histopathological images and virtual slide technologies. These initiatives created the conditions for a broader adoption of computer-aided diagnosis based on whole slide images (WSI) with the hope of a possible contribution to decreasing inter-observer variability. Beside this, automatic image analysis algorithms represent a very promising solution to support pathologist’s laborious tasks during the diagnosis process. Similarly, in order to reduce inter-observer variability between AP reports of malignant tumours, the College of American Pathologists edited 67 organ-specific Cancer Checklists and associated Protocols (CAP-CC&amp;P). Each checklist includes a set of AP observations that are relevant in the context of a given organ-specific cancer and have to be reported by the pathologist. The associated protocol includes interpretation guidelines for most of the required observations. All these changes and initiatives bring up a number of scientific challenges such as the sustainable management of the available semantic resources associated to the diagnostic interpretation of AP images by both humans and computers. In this context, reference vocabularies and formalization of the associated knowledge are especially needed to annotate histopathology images with labels complying with semantic standards. In this research work, we present our contribution in this direction. We propose a sustainable way to bridge the content, features, performance and usability gaps between histopathology and WSI analysis
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Crispo, Manuela. "Utilisation d'une approche multidisciplinaire pour déterminer l'étiologie de syndromes cliniques chez une espèce aviaire menacée : l'exemple de l'Outarde Houbara." Electronic Thesis or Diss., Université de Toulouse (2023-....), 2024. http://www.theses.fr/2024TLSEP058.

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Dans le travail présenté ici, nous avons évalué l’intérêt une approche diagnostique multidisciplinaire pour l’investigation d’entités pathologiques mal caractérisées en utilisant l’Outarde Houbara comme espèce modèle. Cette espèce fait l’objet de plusieurs projets d’élevages conservatoires en Afrique du Nord, au Moyen Orient et en Asie centrale. Nous nous sommes intéressés à trois entités pathologiques ayant toutes le potentiel de mettre en péril les efforts de conservation : l’influenza aviaire hautement pathogène (IAHP), les infections génitales chez les oiseaux inséminés artificiellement et un syndrome respiratoire affectant les oiseaux élevés à l’extérieur et devant à terme renforcer les populations sauvages. Pour la première entité, nous avons validé l’utilisation de l’hybridation in situ par RNAscope pour détecter le gène de matrice des virus influenza aviaires dans des tissus fixés au formol et inclus en paraffine. Cela nous a permis de décrire de manière exhaustive et pour la première fois un épisode infectieux à virus IAHP H5N8 chez l’Outarde Houbara, qui s’est manifestée par des formes cliniques suraigues à aigues de la maladie, associées à un pantropisme tissulaire, avec endothéliotropisme et neurotropisme viral. Pour la seconde entité pathologique, nous avons caractérisé une série de cas de péritonite et salpingo-péritonie associés à des infections par Escherichia coli. La diversité des profils de virulence de la bactérie, identifiée par biologie moléculaire, suggère l’implication de nombreuses souches. Les formes chroniques étaient prédominantes et une infection ascendante a été suspectée. De plus, l’examen histologique a permis l’identification de modifications tissulaires compatibles avec une hyperplasie cystique endométriale, pouvant intervenir comme facteur de risque dans le développement des infections génitales chez l’Houbara. Enfin, pour la troisième entité pathologique, nous nous sommes concentrés sur un syndrome respiratoire multifactoriel d’évolution essentiellement chronique. Divers agents pathogènes ont été détectés chez les oiseaux affectés, y compris une espèce potentiellement nouvelle de Mycoplasme. Des facteurs environnementaux, comme le stress thermique et l’exposition à des tempêtes de sable sont considérés comme des facteurs contributifs importants. Nous avons montré dans ce travail que nous améliorions considérablement le diagnostic étiologique des affections émergentes et réémergentes chez l’Outarde Houbara par une approche multidisciplinaire. Cette approche devrait être encouragée pour étudier la santé d’autres espèces menacées, notamment lors d’une disponibilité limitée en échantillons<br>In the present work, we assessed the use of a multidisciplinary diagnostic approach to successfully investigate poorly characterized pathological entities using an endangered avian species as a model: the Houbara Bustard. This species is the object of several captive breeding operations located in North Africa, the United Arab Emirates and Central Asia. We focused our attention on three conditions that could potentially jeopardize conservation efforts: high pathogenicity avian influenza (HPAI), genital infections in artificially-inseminated breeders and a respiratory syndrome affecting outdoor birds destined to be released. For the first condition, we successfully validated an RNA scope in situ hybridization (ISH) assay for the detection of the avian influenza A virus matrix gene in formalin-fixed and paraffin-embedded (FFPE) tissues. We then provided the first comprehensive description of HPAI H5N8 natural infection in the Houbara, resulting in hyperacute and acute forms exhibiting marked tissue pantropism, endotheliotropism and neurotropism. For the second condition we characterized a series of cases of peritonitis and salpingo-peritonitis. Chronic forms predominated and an ascending infection was highly suspected. Most of the cases were associated with the isolation of Escherichia coli. The identification of a variety of virulence profiles by molecular analysis of selected bacterial isolates suggested the involvement of multiple strains. Furthermore, histopathology allowed the identification of changes consistent with cystic oviductal hyperplasia, expanding the list of potential risk factors involved in the development of genital infections in the Houbara Bustard.For the third condition, we were able to shed some light on a multifactorial respiratory syndrome, focusing on long-lasting, chronic forms. A variety of viral and bacterial pathogens were detected, including potentially a novel Mycoplasma species. Environmental conditions, such as heat stress and exposure to dust storms, were considered significant contributing factors. We showed that combining classical and novel diagnostic tools we were able to significantly improve the etiological diagnosis of emerging and re-merging conditions in the Houbara. This approach should be promoted to study sanitary issues in other endangered species, characterized by a limited availability of samples
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30

Liais, Etienne. "Identification et caractérisation de virus aviaires par des approches de séquençage à haut débit." Thesis, Toulouse, INPT, 2014. http://www.theses.fr/2014INPT0134/document.

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En médecine humaine et vétérinaire, les agents pathogènes représentent la cause de mortalité principale à travers la planète. Les méthodes de diagnostic de ces pathogènes ont considérablement changé et évolué particulièrement depuis l’apparition du séquençage haut débit. Les nouvelles méthodes de séquençage massif ont considérablement diminué le prix d’une séquence permettant de rendre accessible cette technologie révolutionnaire. Dans le cadre de mes travaux de thèse, nous avons mis en place un protocole pour l’utilisation du séquençage Illumina® (avec le séquenceur MiSeq) comme méthode de diagnostic lors de différents cas pathologiques aviaires. L’utilisation de cette méthode nous a permis dans un premier temps d’identifier l’agent étiologique de la maladie foudroyante de la pintade. Cette étude nous a permis de valider l’utilisation de ce genre de méthode pour des cas ciblés, ici lors d’un épisode clinique particulier n’impliquant vraisemblablement qu’un seul candidat pathogène. Ce nouveau coronavirus a fait l’objet d’études complémentaires afin de le caractériser. Nous avons élargis les cibles recherchées en analysant dans un deuxième temps l’ensemble des virus ARN chez le canard lors d’épisodes cliniques respiratoires et/ou de chute de ponte. L’analyse des données a mis en évidence une importante diversité virale et a permis d’identifier des candidats responsables potentiels. L’ensemble des résultats obtenus nous permet de valider l’utilisation du séquençage à haut débit comme un outil puissant de diagnostic<br>Infectious diseases are considered the most prevalent cause of mortality in humans as well as other animals worldwide. Since the advent of high throughput sequencing technologies, diagnostic methods for these conditions have quickly changed and evolved, as the continuously decreasing cost of mass sequencing is making this tool available to larger numbers of people. As part of my thesis project, an Illumina®-based sequencing method (on a MiSeq machine) was designed for diagnostic purposes in clinical cases in poultry. We first used this method to identify the causative agent of the fulminating disease of guinea fowl. This validated the use of our protocol to identify the pathogenic infectious agent behind a specific condition. This newly identified Coronavirus was further analysed and characterised. In a second study we used an unbiased mass sequencing approach to describe the RNA virus populations present in the duck respiratory tract during clinical episodes (respiratory illness or egg drops). Data showed an important viral diversity and we identified some candidate pathogens. Taken together, these results validate the use of high throughput sequencing as a powerful diagnostic tool
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Donfack, Guefack Sidoine Pierre V. "Modélisation des signes dans les ontologies biomédicales pour l'aide au diagnostic." Phd thesis, Université Rennes 1, 2013. http://tel.archives-ouvertes.fr/tel-01057310.

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Introduction : Établir un diagnostic médical fiable requiert l'identification de la maladie d'un patient sur la base de l'observation de ses signes et symptômes. Par ailleurs, les ontologies constituent un formalisme adéquat et performant de représentation des connaissances biomédicales. Cependant, les ontologies classiques ne permettent pas de représenter les connaissances liées au processus du diagnostic médical : connaissances probabilistes et connaissances imprécises et vagues. Matériel et méthodes : Nous proposons des méthodes générales de représentation des connaissances afin de construire des ontologies adaptées au diagnostic médical. Ces méthodes permettent de représenter : (a) Les connaissances imprécises et vagues par la discrétisation des concepts (définition de plusieurs catégories distinctes à l'aide de valeurs seuils ou en représentant les différentes modalités possibles). (b) Les connaissances probabilistes (les sensibilités et les spécificités des signes pour les maladies, et les prévalences des maladies pour une population donnée) par la réification des relations ayant des arités supérieures à 2. (c) Les signes absents par des relations et (d) les connaissances liées au processus du diagnostic médical par des règles SWRL. Un moteur d'inférences abductif et probabiliste a été conçu et développé. Ces méthodes ont été testées à l'aide de dossiers patients réels. Résultats : Ces méthodes ont été appliquées à trois domaines (les maladies plasmocytaires, les urgences odontologiques et les lésions traumatiques du genou) pour lesquels des modèles ontologiques ont été élaborés. L'évaluation a permis de mesurer un taux moyen de 89,34% de résultats corrects. Discussion-Conclusion : Ces méthodes permettent d'avoir un modèle unique utilisable dans le cadre des raisonnements abductif et probabiliste, contrairement aux modèles proposés par : (a) Fenz qui n'intègre que le mode de raisonnement probabiliste et (b) García-crespo qui exprime les probabilités hors du modèle ontologique. L'utilisation d'un tel système nécessitera au préalable son intégration dans le système d'information hospitalier pour exploiter automatiquement les informations du dossier patient électronique. Cette intégration pourrait être facilitée par l'utilisation de l'ontologie du système.
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Sousa, Melo Saulo Leonardo. "The impact on diagnostic yield of the scan mode of cone beam CT images in artificial external root resorption." Thesis, University of Iowa, 2016. https://ir.uiowa.edu/etd/6292.

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Introduction: Root resorption is an undesired but frequent side effect of orthodontic treatment. Several studies have already aimed to evaluate the performance of CBCT on this topic. However, none have addressed the peculiarities of the most common daily orthodontic scenario. The aim of the study was to evaluate the influence of CBCT scans on the diagnosis of artificial external root resorption in the apical third of anterior teeth. Materials and methods: One hundred extracted human anterior teeth were randomly assigned to 2 uneven groups (51 as the control and 49 as the experimental group). A limited area of the apical third of the root of the teeth of the experimental group was selected and a buffer solution was used to induce tooth subsurface demineralization. Before CBCT image acquisition, each tooth was coated with an approximately 0.3 mm thick layer of utility wax to simulate the radiographic appearance of the periodontal space and placed into an empty mandibular anterior socket of a partially edentulous dry human mandible. The mandible was placed into a polystyrene box filled with water prior to the CBCT examination to simulate soft-tissue attenuation and scattering. The CBCT images were obtained on an i-CAT unit (i-CAT Next Generation, Imaging Sciences International, Hatfield, PA) according to three protocols: (I) half scan (180°), 0.40 mm voxel size; (II) full scan (360°), 0.40 mm voxel size; and (III) full scan (360°), 0.125 mm voxel size. The 300 resultant CBCT DICOM volumes were imported into InVivo software (InVivo5, Anatomage, San Jose, CA) for evaluation by three blinded, previously calibrated observers using a five-point confidence rating scale. Cohen’s kappa was used to calculate observers’ agreement. The diagnostic values of sensitivity (Sn), specificity (Sp) and accuracy (Ac) were performed by pooling observer responses for every image modality. Receiver operating characteristic (ROC) were built and the areas under the curve (AUC) were calculated. The Sn, Sp and Ac values were compared by Cochran’s Q test. The AUC values were compared by Mann-Whitney U test. Results: The observers’ agreement ranged from 0.63 to 0.71, which was interpreted as a substantial agreement. Protocol III (0.125 mm voxel size) displayed the highest Sn (81.63 %), Ac (80.67%) and AUC (0.807). There were statistically significant differences between protocol III and the other two protocols (p < 0.001). The specificity of protocol I (84.97 %) was greater than that of protocols II (69.93 %) and III (79.74 %); however statistically significant difference was only found between protocols I and II (p = 0.005). Conclusion: Although there was no difference in accuracy between the degrees of rotation (half and full scan) within the same voxel size (0.4 mm), there was a considerable difference between those and the smallest voxel size (0.125 mm). In fact, it may be suggested that a more dedicated, high resolution scan should be acquired when one intends to investigate the early stage of external root resorption during orthodontic treatment.
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33

Ramsay, Alan Drummond. "Quality control and quality assurance in histopathology : the development and in-use assessment of a multi-parameter audit system for diagnostic surgical pathology." Thesis, University of Southampton, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.242416.

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34

Garnier, Mickaël. "Modèles descriptifs de relations spatiales pour l'aide au diagnostic d'images biomédicales." Thesis, Paris 5, 2014. http://www.theses.fr/2014PA05S015/document.

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La pathologie numérique s’est développée ces dernières années grâce à l’avancée récente des algorithmes d’analyse d’images et de la puissance de calcul. Notamment, elle se base de plus en plus sur les images histologiques. Ce format de données a la particularité de révéler les objets biologiques recherchés par les experts en utilisant des marqueurs spécifiques tout en conservant la plus intacte possible l’architecture du tissu. De nombreuses méthodes d’aide au diagnostic à partir de ces images se sont récemment développées afin de guider les pathologistes avec des mesures quantitatives dans l’établissement d’un diagnostic. Les travaux présentés dans cette thèse visent à adresser les défis liés à l’analyse d’images histologiques, et à développer un modèle d’aide au diagnostic se basant principalement sur les relations spatiales, une information que les méthodes existantes n’exploitent que rarement. Une technique d’analyse de la texture à plusieurs échelles est tout d’abord proposée afin de détecter la présence de tissu malades dans les images. Un descripteur d’objets, baptisé Force Histogram Decomposition (FHD), est ensuite introduit dans le but d’extraire les formes et l’organisation spatiale des régions définissant un objet. Finalement, les images histologiques sont décrites par les FHD mesurées à partir de leurs différents types de tissus et des objets biologiques marqués qu’ils contiennent. Les expérimentations intermédiaires ont montré que les FHD parviennent à correctement reconnaitre des objets sur fonds uniformes y compris dans les cas où les relations spatiales ne contiennent à priori pas d’informations pertinentes. De même, la méthode d’analyse de la texture s’avère satisfaisante dans deux types d’applications médicales différents, les images histologiques et celles de fond d’œil, et ses performances sont mises en évidence au travers d’une comparaison avec les méthodes similaires classiquement utilisées pour l’aide au diagnostic. Enfin, la méthode dans son ensemble a été appliquée à l’aide au diagnostic pour établir la sévérité d’un cancer via deux ensembles d’images histologiques, un de foies métastasés de souris dans le contexte du projet ANR SPIRIT, et l’autre de seins humains dans le cadre du challenge CPR 2014 : Nuclear Atypia. L’analyse des relations spatiales et des formes à deux échelles parvient à correctement reconnaitre les grades du cancer métastasé dans 87, 0 % des cas et fourni des indications quant au degré d’atypie nucléaire. Ce qui prouve de fait l’efficacité de la méthode et l’intérêt d’encoder l’organisation spatiale dans ce type d’images particulier<br>During the last decade, digital pathology has been improved thanks to the advance of image analysis algorithms and calculus power. Particularly, it is more and more based on histology images. This modality of images presents the advantage of showing only the biological objects targeted by the pathologists using specific stains while preserving as unharmed as possible the tissue structure. Numerous computer-aided diagnosis methods using these images have been developed this past few years in order to assist the medical experts with quantitative measurements. The studies presented in this thesis aim at adressing the challenges related to histology image analysis, as well as at developing an assisted diagnosis model mainly based on spatial relations, an information that currently used methods rarely use. A multiscale texture analysis is first proposed and applied to detect the presence of diseased tissue. A descriptor named Force Histogram Decomposition (FHD) is then introduced in order to extract the shapes and spatial organisation of regions within an object. Finally, histology images are described by the FHD measured on their different types of tissue and also on the stained biological objects inside every types of tissue. Preliminary studies showed that the FHD are able to accurately recognise objects on uniform backgrounds, including when spatial relations are supposed to hold no relevant information. Besides, the texture analysis method proved to be satisfactory in two different medical applications, namely histology images and fundus photographies. The performance of these methods are highlighted by a comparison with the usual approaches in their respectives fields. Finally, the complete method has been applied to assess the severity of cancers on two sets of histology images. The first one is given as part of the ANR project SPIRIT and presents metastatic mice livers. The other one comes from the challenge ICPR 2014 : Nuclear Atypia and contains human breast tissues. The analysis of spatial relations and shapes at two different scales achieves a correct recognition of metastatic cancer grades of 87.0 % and gives insight about the nuclear atypia grade. This proves the efficiency of the method as well as the relevance of measuring the spatial organisation in this particular type of images
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35

Favre-Besse, Franck-Cyril. "Modulateurs du transport vésiculaire du glutamate : développement d'outils pharmacologiques et de diagnostic pour la maladie d'Alzheimer." Phd thesis, Université René Descartes - Paris V, 2012. http://tel.archives-ouvertes.fr/tel-00923157.

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Les transporteurs vésiculaires du glutamate (VGLUTs) sont impliqués dans la recapture du glutamate du cytosol vers les vésicules présynaptiques. Depuis leurs caractérisations récentes en 2000, leurs implications dans plusieurs maladies neurodégénératives ont été démontrées. Ils jouent ainsi un rôle primordial dans la transmission nerveuse glutamatergique. Deux colorants naturels, le Rose Bengale et le Bleu Trypan, restent les meilleurs inhibiteurs connus à ce jour, avec respectivement des CI50 de 25 et 50 nM. Dans un premier temps, nous avons conçu et optimisé une série d'analogues basée sur le synthon Rose Bengale (inhibiteur non-compétitif). Ce travail a notamment permis de mettre en évidence l'effet des formes tautomères (quinone et lactone) sur l'inhibition des VGLUTs. Ainsi la forme quinonique, présente à pH physiologique, a été confirmée comme étant la seule capable de bloquer la recapture du glutamate. Dans un second temps, nous nous sommes intéressés à la famille du Bleu Trypan (inhibiteur compétitif) et nous avons déterminé la structure minimale active avec l'objectif de rendre ces molécules plus " drug-like ". En effet, l'intérêt de ce projet est de développer de petites structures aisément radiomarquables pour une utilisation dans un contexte physio-pathologique.
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36

Feng, Gang. "Etude de nouveaux marqueurs moléculaires pour le diagnostic précoce et le pronostic des cancers." Phd thesis, Université Jean Monnet - Saint-Etienne, 2010. http://tel.archives-ouvertes.fr/tel-00672376.

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Le but de notre étude était d'évaluer si les marqueurs moléculaire pourrait détecter de façon sensible et pour aider à un diagnostic précoce et améliorer la survie des patients avec CCR. Dans ce travail, nous avons utilisé les méthodes courantes telles que la spectrométrie, la PCR, l'ELISA et PicoGreen® pour évaluer l'ADN circulant, l'intégrité de l'ADN circulante, l'ARN circulant, l'ARNm CA9 sérique, et la protéine CA9 circulant pour le diagnostic ou le suivi des CCR. Le niveau d'ARN sérique et celui d'ARNm CA9 sérique chez les patients atteints de CRCC sont plus élevés que chez les témoins sains. Chez les patients atteints de CRCC, le niveau de l'ARN circulant est indépendant de l'âge, du sexe, du stade TNM, du grade Fuhrman, et de la taille de la tumeur. Le niveau de l'ARNm CA9 sérique est indépendant de l'âge, du sexe et du grade Fuhrman, mais est corrélé au stade TNM, à la présence de métastases et à la taille de la tumeur. Selon nos résultats, l'ARN circulant et l'ARNm CA9 sérique peuvent être utilisés comme biomarqueurs diagnostiques du CRCC. Par spectrométrie et par la méthode PicoGreen®, la moyenne de l'ADN sérique chez les patients atteints de CRCC était plus élevée que chez les témoins sains, mais cette différence n'était pas significative. Nos résultats indiquent que la sensibilité et la spécificité de l'ADN sérique ne sont pas satisfaisantes pour le diagnostic de CCR. En outre, l'intégrité de l'ADN sérique chez les patients atteints de CRCC était meilleure que chez les patients atteints d'oncocytome rénal et que chez les témoins sains. L'intégrité de l'ADN dans le sérum pourrait constituer un marqueur pour le diagnostic de CRCC. Le niveau de la protéine CA9 chez les patients atteints de CRCC métastatique était plus élevé que chez les patients atteints de CRCC localisé et que chez les témoins sains. Le niveau élevé de la protéine CA9 suggère un risque élevé de récidive. La protéine CA9 sérique pourrait être utilisé pour guider le suivi post opératoire et peut être dans l'avenir indiquer un traitement adjuvant précoce des patients du groupe à haut risque de récidive
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37

Garnier, Mickaël. "Modèles descriptifs de relations spatiales pour l'aide au diagnostic d'images biomédicales." Electronic Thesis or Diss., Paris 5, 2014. http://www.theses.fr/2014PA05S015.

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La pathologie numérique s’est développée ces dernières années grâce à l’avancée récente des algorithmes d’analyse d’images et de la puissance de calcul. Notamment, elle se base de plus en plus sur les images histologiques. Ce format de données a la particularité de révéler les objets biologiques recherchés par les experts en utilisant des marqueurs spécifiques tout en conservant la plus intacte possible l’architecture du tissu. De nombreuses méthodes d’aide au diagnostic à partir de ces images se sont récemment développées afin de guider les pathologistes avec des mesures quantitatives dans l’établissement d’un diagnostic. Les travaux présentés dans cette thèse visent à adresser les défis liés à l’analyse d’images histologiques, et à développer un modèle d’aide au diagnostic se basant principalement sur les relations spatiales, une information que les méthodes existantes n’exploitent que rarement. Une technique d’analyse de la texture à plusieurs échelles est tout d’abord proposée afin de détecter la présence de tissu malades dans les images. Un descripteur d’objets, baptisé Force Histogram Decomposition (FHD), est ensuite introduit dans le but d’extraire les formes et l’organisation spatiale des régions définissant un objet. Finalement, les images histologiques sont décrites par les FHD mesurées à partir de leurs différents types de tissus et des objets biologiques marqués qu’ils contiennent. Les expérimentations intermédiaires ont montré que les FHD parviennent à correctement reconnaitre des objets sur fonds uniformes y compris dans les cas où les relations spatiales ne contiennent à priori pas d’informations pertinentes. De même, la méthode d’analyse de la texture s’avère satisfaisante dans deux types d’applications médicales différents, les images histologiques et celles de fond d’œil, et ses performances sont mises en évidence au travers d’une comparaison avec les méthodes similaires classiquement utilisées pour l’aide au diagnostic. Enfin, la méthode dans son ensemble a été appliquée à l’aide au diagnostic pour établir la sévérité d’un cancer via deux ensembles d’images histologiques, un de foies métastasés de souris dans le contexte du projet ANR SPIRIT, et l’autre de seins humains dans le cadre du challenge CPR 2014 : Nuclear Atypia. L’analyse des relations spatiales et des formes à deux échelles parvient à correctement reconnaitre les grades du cancer métastasé dans 87, 0 % des cas et fourni des indications quant au degré d’atypie nucléaire. Ce qui prouve de fait l’efficacité de la méthode et l’intérêt d’encoder l’organisation spatiale dans ce type d’images particulier<br>During the last decade, digital pathology has been improved thanks to the advance of image analysis algorithms and calculus power. Particularly, it is more and more based on histology images. This modality of images presents the advantage of showing only the biological objects targeted by the pathologists using specific stains while preserving as unharmed as possible the tissue structure. Numerous computer-aided diagnosis methods using these images have been developed this past few years in order to assist the medical experts with quantitative measurements. The studies presented in this thesis aim at adressing the challenges related to histology image analysis, as well as at developing an assisted diagnosis model mainly based on spatial relations, an information that currently used methods rarely use. A multiscale texture analysis is first proposed and applied to detect the presence of diseased tissue. A descriptor named Force Histogram Decomposition (FHD) is then introduced in order to extract the shapes and spatial organisation of regions within an object. Finally, histology images are described by the FHD measured on their different types of tissue and also on the stained biological objects inside every types of tissue. Preliminary studies showed that the FHD are able to accurately recognise objects on uniform backgrounds, including when spatial relations are supposed to hold no relevant information. Besides, the texture analysis method proved to be satisfactory in two different medical applications, namely histology images and fundus photographies. The performance of these methods are highlighted by a comparison with the usual approaches in their respectives fields. Finally, the complete method has been applied to assess the severity of cancers on two sets of histology images. The first one is given as part of the ANR project SPIRIT and presents metastatic mice livers. The other one comes from the challenge ICPR 2014 : Nuclear Atypia and contains human breast tissues. The analysis of spatial relations and shapes at two different scales achieves a correct recognition of metastatic cancer grades of 87.0 % and gives insight about the nuclear atypia grade. This proves the efficiency of the method as well as the relevance of measuring the spatial organisation in this particular type of images
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38

Michaud, Bénédicte. "Etude de la réponse lymphocytaire T dans l'allergie de l'enfant, au diagnostic et au cours de la désensibilisation." Phd thesis, Université René Descartes - Paris V, 2013. http://tel.archives-ouvertes.fr/tel-00881757.

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Les maladies allergiques sont de plus en plus fréquentent. Elles atteignent souvent l'enfant jeune chez qui l'allergie respiratoire et l'allergie alimentaire sont les principales pathologies. L'unique traitement curatif est l'immunothérapie spécifique d'antigène (ITA), largement développée dans l'allergie respiratoire et encore à ses débuts dans l'allergie alimentaire. Pour adapter au mieux la prise en charge du patient, le diagnostic précis de l'allergie est indispensable et il n'existe actuellement pas d'examen biologique totalement fiable. Seul, la présence d'IgE spécifiques permet de diagnostiquer une sensibilisation à un allergène mais pas une allergie cliniquement symptomatique. Dans une première partie, nous avons étudié l'intérêt d'un test fonctionnel, l'ELISpot (Enzyme-linked immunosorbent spot), dans le diagnostic de l'allergie aux acariens chez l'enfant asthmatique. Le nombre de lymphocytes T circulants spécifiques d'acariens sécréteur d'interleukine (IL)-4 ou d'IL-13 était associé à la présence d'une allergie symptomatique, indépendamment des IgE spécifiques. Il était plus élevé dans le cas d'une rhinite allergique sévère et plus faible dans le cas d'une rhinite allergique légère. De plus, il variait au cours de l'année en fonction des saisons avec un pic en automne et un pic en début de printemps. Dans une deuxième partie, nous avons étudié l'intérêt de l'ELISpot dans le diagnostic de l'allergie au lait de vache chez l'enfant, confirmée par un test de provocation orale en double aveugle. Nous avons décrit que le nombre de lymphocytes T spécifiques de la caséine et sécréteurs d'IL-4 et d'IL-13 était associé à l'allergie au lait de vache avec une sensibilité de 100%. Par ailleurs, le nombre de lymphocytes T spécifiques de la caséine était également associé à la dose maximale de lait tolérée par l'enfant.Enfin, dans une troisième partie, nous avons étudié la réponse lymphocytaire T au cours d'une ITA sub-linguale (SLIT) d'une part et sous-cutanée (SCIT) d'autre part, chez des enfants asthmatiques allergiques aux acariens suivis pendant une année. Nous avons décrit une diminution des lymphocytes Th2 (sécréteurs d'IL-4 et IL-13) spécifiques d'acariens après 12 mois de SLIT associée à une augmentation des cellules sécrétrices d'IL-10 (Tr1) spécifiques d'acariens après 6 mois de SLIT. De plus, les lymphocytes T régulateurs (CD4+CD25hiCD127loFoxp3+) étaient augmentés après 12 mois de SCIT. Nous n'avons pas retrouvé de production accrue d'interféron γ (IFNγ) par les lymphocytes T spécifiques d'acariens au cours de la désensibilisation.Au total, ce travail nous a permis de décrire qu'un test fonctionnel, l'ELISpot, permet de réaliser un diagnostic fiable de l'allergie aux acariens et de l'allergie au lait de vache chez l'enfant. Par ailleurs, l'ITA induit une diminution des cellules Th2 et une augmentation des cellules Tr1 par voie sub-linguale ainsi qu'une augmentation des Treg Foxp3+ par voie sous-cutanée sans immunodéviation Th2/Th1, chez l'enfant allergique aux acariens.
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39

Keren, Boris. "La déficience intellectuelle : du diagnostic en puces ADN à l'identification de gènes candidats." Phd thesis, Université René Descartes - Paris V, 2013. http://tel.archives-ouvertes.fr/tel-00918306.

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L'analyse chromosomique sur puce ADN (ACPA) tend à devenir le principal examen diagnostique dans la déficience intellectuelle (DI). Parmi les techniques d'ACPA, les puces SNP ont l'intérêt de pouvoir détecter les pertes d'hétérozygotie, et par conséquent d'identifier les isodisomies uniparentales (iUPD) et les zones d'identité liées à la consanguinité. Nous avons étudié une cohorte de 1 187 patients atteints de DI, dans un cadre diagnostique, sur puces SNP. Nous avons réalisé, par cette étude, 145 diagnostics (12%) dont 2 iUPD et 6 délétions n'incluant qu'un seul gène. De plus, nous avons détecté 639 CNV rares non décrits chez des sujets contrôles et incluant des séquences codantes, ce qui nous a permis d'identifier 11 gènes candidats dans la DI : CAMTA1, SP3, CNTNAP4, NUDT12, STXBP6, DOCK8, DOCK10, SMARCA2, NYAP2, ATAD3A et ATAD3B. Nous avons tenté de valider l'implication de ces gènes par séquençage, mais n'avons trouvé de seconde mutation pour aucun d'entre eux. Toutefois, des réarrangements de CAMTA1 ont été retrouvés dans 2 autres familles avec un phénotype homogène (DI et ataxie congénitale) ce qui nous a permis d'affirmer qu'il s'agit d'un gène de DI. Par ailleurs, l'homozygosity mapping, réalisé avec puces SNP, a identifié, par séquençage whole exome, une mutation non-sens homozygote du gène BUD13 dans une famille de DI syndromique. Enfin, de façon fortuite, nous avons caractérisé en ACPA une translocation familiale entraînant une disruption d'un gène d'ataxie spino-cérébelleuse, ATXN10, ce qui a permis de mieux comprendre la physiopathologie de cette maladie. Au total, notre étude démontre l'intérêt des puces SNP dans la DI, d'une part en diagnostic et d'autre part pour l'identification de nouveaux gènes responsables de DI.
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40

Zhao, An. "Etude des petits ARNs extracellulaires pour le diagnostic de cancer du rein à cellules claires." Phd thesis, Université Jean Monnet - Saint-Etienne, 2013. http://tel.archives-ouvertes.fr/tel-00999237.

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Le cancer du rein est un problème majeur de santé publique. Un diagnostic précoce améliore les chances de survie. Le diagnostic repose essentiellement sur les examens d'imagerie comme l'échographie, la tomodensitométrie et l'IRM. Ces examens sont parfois associés à la biopsie et sont couteux et parfois invasifs. De plus, l'imagerie n'est pas capable de faire la distinction entre les tumeurs bénignes et les tumeurs malignes et entre les sous-types histologiques de carcinome à cellules claires qui est le plus fréquent. Il n'existe pas dans le cancer rénal de marqueur comme la PSA dans le cancer de la prostate ou la Foetoprotéine et l'HCG dans le cancer du testicule. Le but de cette étude est concentré sur la recherche des marqueurs mARNs ou miARNs dans les liquides biologiques (sérum, plasma, urine) pour le cancer du rein à cellules claires. Nous avons montré que les petits ARNs dans le sérum et les urines et l'intégrité des ARNs dans les urines étaient des outils diagnostiques dans le cancer du rein à cellules claires. Si ces petits ARNs circulants sont validés, on peut éventuellement imaginer l'intérêt pratique en clinique comme la détection des petits ARNs circulants dans l'urine pour prédire le cancer, la classification de la tumeur pour aider le clinicien, la prédiction d'une récidive ou d'une progression soit après néphrectomie soit au cours d'un traitement médical
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41

Medeiros, Felipe de Araujo Andrade. "Comparação de métodos de imagem do disco óptico e da camada de fibras nervosas da retina para o diagnóstico do glaucoma." Universidade de São Paulo, 2005. http://www.teses.usp.br/teses/disponiveis/5/5149/tde-14102014-163044/.

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Alterações no aspecto do disco óptico e da camada de fibras nervosas da retina (CFN) freqüentemente precedem o aparecimento de defeitos de campo visual no glaucoma, o que faz com que a avaliação destas estruturas seja essencial para o diagnóstico precoce e prevenção da perda visual nesta doença. A polarimetria de varredura a laser (GDx VCC), a oftalmoscopia confocal de varredura a laser (HRT II [Heidelberg Retina Tomograph]) e a tomografia de coerência óptica (Stratus OCT) são tecnologias que permitem a avaliação objetiva e quantitativa do disco óptico e da CFN. No presente estudo, estas tecnologias foram comparadas em sua habilidade para diferenciar pacientes glaucomatosos de indivíduos normais. Pacientes com glaucoma foram selecionados com base na presença de defeitos reprodutíveis de campo visual na perimetria acromática automatizada (glaucoma perimétrico), ou com base na evidência documentada de progressão do dano glaucomatoso ao disco óptico, sem presença de defeitos de campo visual (glaucoma pré-perimétrico). Indivíduos normais apresentaram campos visuais e exame clínico dentro da normalidade. Todos os indivíduos foram submetidos a exames com o GDx VCC, HRT II, Stratus OCT e campo visual dentro de um período de três meses. Diversas medidas foram utilizadas para avaliação da acurácia diagnóstica, incluindo áreas sob as curvas receiver operating characteristic (AROC), sensibilidades para especificidades fixas, e razões de probabilidade. Modelos estatísticos foram utilizados para avaliação da influência da severidade do glaucoma e tamanho do disco óptico na performance diagnóstica dos diferentes instrumentos. Um olho de cada indivíduo foi utilizado para análise. Dos 258 sujeitos inicialmente avaliados, 33 (13%) foram posteriormente excluídos por apresentarem imagens de baixa qualidade em pelo menos um dos aparelhos, restando 225 indivíduos (133 glaucomatosos e 92 normais) para análise. Na comparação entre os parâmetros de cada instrumento com maiores valores de AROC, o parâmetro do GDx VCC, Nerve Fiber Indicator (NFI; AROC = 0,91), e o parâmetro do Stratus OCT, Espessura Média (AROC = 0,90), apresentaram áreas sob as curvas ROC significativamente superiores à do parâmetro do HRT II, função discriminante de Bathija (AROC = 0,84). A severidade do defeito de campo visual exerceu influência significativa sob a acurácia diagnóstica dos três instrumentos, com melhora no poder diagnóstico em casos mais avançados da doença. Para o GDx VCC e Stratus OCT, o aumento no tamanho do disco óptico foi associado à diminuição na sensibilidade para detecção do glaucoma; enquanto que, para o HRT II, diminuição no tamanho do disco óptico foi associada à diminuição na sensibilidade. Razões de probabilidade para resultados anormais nas xxv classificações finais de cada instrumento foram associadas a grandes efeitos de mudança na probabilidade pós-teste em relação à probabilidade préteste, sugerindo que o encontro de um resultado anormal em qualquer um destes testes, durante a avaliação de um paciente com suspeita de glaucoma, tem impacto significativo em aumentar a probabilidade de que a doença esteja presente. Além disso, os resultados obtidos na avaliação de pacientes com glaucoma pré-perimétrico sugerem que todos os três instrumentos sejam capazes de detectar alterações estruturais precoces no glaucoma, antes do aparecimento de defeitos de campo visual na perimetria acromática<br>Changes in the structural appearance of the optic nerve head (ONH) and retinal nerve fiber layer (RNFL) have been reported to precede the development of visual field loss in glaucoma. Detection of ONH and RNFL damage is therefore crucial for early diagnosis of glaucoma and prevention of functional loss from the disease. Scanning laser polarimetry (GDx VCC), confocal scanning laser ophthalmoscopy (HRT II [Heidelberg Retina Tomograph]) and optical coherence tomography (Stratus OCT) are different technologies capable of providing objective and quantitative information related to these structures. The purpose of the present study was to compare, in a single population, the diagnostic abilities of these technologies in the discrimination of glaucomatous patients from healthy subjects. Glaucoma patients were selected based on the presence of repeatable visual field defects, as identified by standard automated perimetry (perimetric glaucoma), or documented evidence of progressive damage to the optic disc, in the absence of detectable visual field loss (preperimetric glaucoma). Normal subjects had normal visual fields and normal clinical examination. All subjects underwent imaging with the GDx VCC, HRT II and Stratus OCT within a 3-month period. Several measures were used for evaluation of diagnostic accuracy, including the area under the receiver operating characteristic curve (AROC), sensitivities at fixed specifities, and likelihood ratios. Statistical models were used to evaluate the influence of glaucoma severity and optic disc size on the diagnostic performance of the different instruments. One eye of each individual was randomly selected for statistical analysis. From an initial group of 258 eligible subjects, 33 (13%) had images of unacceptable quality, leaving 133 glaucoma patients and 92 healthy subjects for further analysis. In the comparison of the parameters with highest values of AROC from each instrument, the GDx VCC Nerve Fiber Indicator (AROC = 0.91) and the Stratus OCT Average Thickness (AROC = 0.90) perfomed significanlty better than the HRT II Bathija discriminant function (AROC = 0.84). For all instruments, the diagnostic accuracy increased with increasing severity of visual field defects. For the GDx VCC and Stratus OCT parameters, an increase in the size of the optic disc was related to a decrease in the sensitivity for glaucoma detection. An opposite effect was observed with the HRT II: a decrease in the size of the optic disc was related to a decrease in the sensitivity for glaucoma diagnosis. Abnormal results for each of the instruments were associated with strong positive likelihood ratios, indicating a large change from prestest to posttest probability of glaucoma. These results suggest that the finding of an abnormal result in any of these tests, when assessing a patient suspect of having glaucoma, would substantially raise the probability of disease. Results of the evaluation of patients with preperimetric glaucoma also suggest that all three instruments are able to detect early glaucomatous structural damage in the absence of visual field loss
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42

Moura, Frederico Castelo. "Comparação das medidas da espessura macular e da camada de fibras nervosas retiniana para detecção de atrofia em banda do nervo óptico através da tomografia de coerência óptica." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/5/5149/tde-24012008-132225/.

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Pacientes com compressão quiasmática apresentam perda das fibras nervosas da retina nasal que decussam no quiasma óptico. Por conseguinte, ocorre perda das fibras nervosas, predominantemente, no setor nasal e temporal do disco óptico, que se manifesta por atrofia em banda do nervo óptico ao exame oftalmoscópico e hemianopsia temporal ao exame de campo visual. Trabalhos anteriores mostraram que o tomógrafo de coerência óptica é capaz de diferenciar pacientes com atrofia em banda do nervo óptico associada à hemianopsia temporal completa de indivíduos normais através da análise da camada de fibras nervosas peripapilar. Estudos em glaucoma têm sugerido que a avaliação da espessura macular poderia ser útil na quantificação da perda neural como um método alternativo ou complementar ao estudo da camada de fibras nervosas da retina. No presente estudo, a espessura macular e da camada de fibras nervosas foram avaliadas pelo tomógrafo de coerência óptica em pacientes com atrofia em banda do nervo óptico e graus variados de hemianopsia temporal. O desempenho dos parâmetros maculares para detecção da atrofia em banda do nervo óptico foi avaliado pela área sob a curva ROC (AROC) e sensibilidades para especificidades fixas e os resultados foram comparados aos parâmetros da camada de fibras nervosas peripapilar. Para identificar os parâmetros do Stratus OCT que apresentaram melhor desempenho para diferenciar pacientes com AB do nervo óptico de indivíduos normais, modelos de regressão logística foram utilizados. A correlação estrutura-função foi realizada entre o grau do defeito temporal e os valores de espessura macular e da camada de fibras peripapilar através do coeficiente de correlação de Spearman. A categorização diagnóstica dos parâmetros da camada de fibras nervosas através do banco de dados normativos foi avaliada pelos valores de sensibilidade e especificidade calculados pelo teste exato de Fisher. Quarenta e quatro olhos com atrofia em banda e 47 olhos normais foram avaliados no estudo. Entre os parâmetros maculares, os parâmetros da retina nasal apresentaram melhor desempenho para detectar atrofia em banda do nervo óptico comparados aos parâmetros da retina temporal. Não houve diferença significante (p=0,32) entre as áreas sob a curva ROC do melhor parâmetro macular (AROC=0,97) e do melhor parâmetro da camada de fibras nervosas retiniana (AROC=0,99). Na avaliação da correlação estrutura-função, os parâmetros da retina nasal apresentaram maior correlação com o defeito campimétrico comparados aos parâmetros da camada de fibras nervosas da retinal. Entre os parâmetros maculares, a espessura nasal média apresentou a maior correlação (rs=0,618). Entre os parâmetros da camada de fibras nervosas da retina, a espessura média apresentou a maior correlação (rs=0,479). Os parâmetros espessura média, espessura nasal e espessura temporal da camada de fibras nervosas da retina apresentaram melhor desempenho diagnóstico baseado na categorização diagnóstica do banco de dados normativos. Os resultados obtidos no estudo mostraram que os parâmetros maculares discriminam olhos com atrofia em banda do nervo óptico em pacientes com graus variados de defeito temporal. Além disso, os parâmetros da retina nasal podem colaborar com o exame perimétrico e os parâmetros da camada de fibras nervosas para o seguimento dos pacientes com compressão quiasmática.<br>Patients with chiasmal compression present damage of crossed fibers of nasal retina. Therefore, retinal nerve fiber layer loss occurs predominantly on the nasal and temporal sides of the optic disc, a pattern that can be identified on ophthalmoscopy as band atrophy of the optic nerve and on visual field as temporal hemianopia. Previous studies have been demonstrated that optical coherence tomography is able to detect retinal nerve fiber layer loss in patients with lesions of the optic chiasm and complete temporal hemianopia. Studies in glaucoma have been suggested that macular thickness measurements could be useful in quantification of optical nerve axonal loss as alternative or complement method to evaluate the retinal nerve fiber layer. The purpose of the present study was to compare macular thickness and retinal nerve fiber thickness measurements in patients with band atrophy of the optic nerve and different severities of visual field defect using optical coherence tomography. Area under the receiver operating characteristic curve (AROC) and sensitivities at fixed specificities were performed for evaluation of diagnostic accuracy of macular and retinal nerve fiber layer parameters. To identify the best optical coherence tomography measurements to differentiate band atrophy of the optic nerve patients from normal individuals, logistic regression models were performed. Association between optical coherence tomography parameters and temporal field defect were examined by Spearman coefficient of correlation. Fisher\'s exact test was performed to evaluate diagnostic ability of retinal nerve fiber parameters by optical coherence tomography in eyes with band atrophy using comparison with its internal normative database. A total of 44 eyes with band atrophy of the optic nerve and 47 normal eyes were studied. Among macular parameters, nasal retina measurements showed diagnostic accuracy better than temporal retina measurements. No statistically significant difference (p=0.32) was found between areas under ROC curve for the best macular parameter (AROC=0.97) and the best retinal nerve fiber layer parameter (AROC=0.99). Nasal retina parameters correlations were higher than retinal nerve fiber parameters. The highest correlation was observed for the mean nasal thickness (rs=0.618) for macular parameters. In retinal nerve fiber parameters, the highest correlation was observed for the average thickness (rs=0.479). In evaluation of diagnostic ability of normative database, the average thickness parameter demonstrated the highest sensitivity for detection of abnormalities in eyes with band atrophy, followed by the parameters related to the nasal and temporal quadrants. These results suggest that macular thickness measurements discriminate eyes with band atrophy of the optic nerve with different severities of temporal field defect. Results also suggest that nasal retina thickness measurements could potentially be used to evaluate retinal ganglion cell loss in patients with chiasmal compression.
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43

Van, Rensburg C. J. "Identification of clinically-informative biomarkers within the spectrum of gastro-oesophageal reflux disease in the South African population." Thesis, Link to the online version, 2006. http://hdl.handle.net/10019.1/1150.

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44

Baduel, Sophie. "Du dépistage à la confirmation du diagnostic de trouble du spectre autistique : dispositif, outils et suivi du développement en population tout venant." Phd thesis, Université Toulouse le Mirail - Toulouse II, 2013. http://tel.archives-ouvertes.fr/tel-00996883.

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Les troubles du Spectre Autistique (TSA) sont des troubles neuro-développementaux, d'apparition précoce et qui affectent le développement de l'individu tout au long de sa vie. La prévalence des TSA est estimée aux alentours de 1% de la population générale. Des interventions précoces peuvent minimiser le handicap résultant de ce trouble et améliorer la qualité de vie et l'insertion sociale des enfants. L'opportunité de bénéficier d'une intervention précoce dépend de l'âge du diagnostic. Aujourd'hui, l'âge moyen du diagnostic des TSA en France est de 5 ans en moyenne. Un diagnostic précoce est pourtant possible dès l'âge de 24 mois. Un dépistage précoce des TSA permettrait de diminuer l'âge du diagnostic et par conséquent l'âge du début de l'intervention, maximisant ainsi les bénéfices. L'objectif général de ce travail, organisé autour de 3 études, est de participer à l'amélioration des pratiques de dépistage et de diagnostic précoce des TSA en évaluant la pertinence de différents outils pour aider les professionnels à repérer et orienter les enfants à risque de TSA. La première étude a pour objectif d'évaluer la faisabilité d'un dépistage systématique des TSA chez les enfants âgés de 24 mois. Un dispositif de dépistage a été développé avec pour préalables la formation des professionnels de première ligne et la validation d'outils de dépistage spécifiques aux TSA : le CHAT et le M-CHAT. La seconde étude a pour objectif d'améliorer l'orientation diagnostique des enfants repérés pour une suspicion de TSA. Dans cette optique, cette étude vise à évaluer la pertinence de l'utilisation du module 1 de l'ADOS-G pour confirmer ou infirmer la présence d'un risque de TSA chez les enfants de moins de 3 ans. Enfin, l'objectif de la dernière étude est d'évaluer l'apport éventuel des données issues de l'évaluation développementale dans le dispositif. L'évaluation développementale des enfants permet de mettre en évidence leur profil et ainsi de proposer un plan d'intervention dans l'attente de la confirmation diagnostique. Les résultats de ces études témoignent de la possibilité de repérer les enfants à risque de TSA à 24 mois. Les professionnels impliqués dans la pratique de dépistage ont aujourd'hui à leur disposition deux outils validés sur un échantillon français: le CHAT et le M-CHAT. Ces outils présentent des propriétés psychométriques satisfaisantes pour une utilisation en population générale. L'utilisation du module 1 de l'ADOS-G permet de différencier les enfants de moins de 3 ans présentant un TSA des enfants avec une autre problématique développementale. Cet outil apparaît donc important pour améliorer la spécificité du dépistage précoce. L'évaluation développementale apporte quant à elle des informations sur les profils des enfants avec un TSA, marqués notamment par des déficits dans les domaines de l'imitation et du jeu. Les implications cliniques de ces études sont discutées et de nouvelles pistes de recherche sont proposées.
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45

Zahid, Muhammad. "Design and Optimization of Recombinant Antibodies Directed Against Platelet Glycoprotein VI with Therapeutic and Diagnostic Potentials." Phd thesis, Université Paris Sud - Paris XI, 2011. http://tel.archives-ouvertes.fr/tel-00922980.

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Human platelets glycoprotein VI (GPVI) is evidenced to be a platelet receptor of major importance in the occurrence of arterial thrombosis. Thus, it can be considered to be of great interest in diagnosis and therapeutic of atheriosclerotic diseases. Antibodies are powerful molecules which can be used in both diagnostic as well as for therapeutic purposes due to their unique characteristics. Monoclonal and recombinant antibodies have antigen restricted specificity, high affinity and can be used in various assays. Moreover, the good knowledge of their structure and molecular engineering facilities now allows the antibody modulation according to desired properties.Our group has already produced several monoclonal antibodies to human GPVI by gene gun immunization against the immunoadhesin hGPVI-Fc, which differ in fine epitopespecificity, affinity and other functional properties (Lecut et al. 2003). One, 3J24, with diagnostic potential while the other, 9O12, has a therapeutic potential because it blocks the binding of GPVI to collagen. Its Fab fragment has been extensively characterized in vitro,ex vivo and in vivo for its antithrombotic properties.Here, we designed and reshaped a single-chain antibody fragment (scFv) based on 3J24variable domains for the quantification of GPVI with diagnostic potential. We were also involved in the design, production and functional evaluation of humanized anti-GPVI recombinant antibody fragments (scFvs and Fabs) with therapeutic properties.
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46

Clark, Thomas Justin. "Ambulatory diagnosis of endometrial pathology." Thesis, University of Birmingham, 2003. http://etheses.bham.ac.uk//id/eprint/214/.

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The aim of this thesis was to determine the diagnostic accuracy of outpatient endometrial evaluation using endometrial biopsy (EB), ultrasound scan (USS) and hysteroscopy (OPH) by conducting systematic quantitative reviews of the published literature. The optimum diagnostic strategy in terms of cost-effectiveness (cost per life year gained), was then established for the investigation of women with post-menopausal bleeding (PMB) for endometrial cancer, using the review data in a decision analysis designed to reflect current service provision. Meta-analyses showed that a positive test result following EB or OPH was more useful for predicting endometrial disease than USS, whereas a negative test result following USS was more useful for excluding endometrial disease than EB or OPH. The economic model included 12 diagnostic strategies and indicated that a strategy based on initial diagnosis with USS, using a 5mm double layer endometrial thickness cut-off, was the most cost-effective. Sensitivity analyses showed that initial investigation with EB or USS using a 4mm cut-off were also potentially cost-effective (incremental cost-effectiveness ratios under £30,000 per life year gained) at their most favorable estimates of diagnostic performance, in women under 65 years and at disease prevalence of 10% or more. The choice between initial testing with EB or USS will therefore depend upon patient age and preference, disease prevalence and the availability of high quality USS. In most circumstances women presenting for the first time with PMB should undergo initial evaluation with pelvic ultrasound using a threshold of 4mm or 5mm to define abnormal results.
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47

Ismaili, Khalid. "Evaluation et prise en charge des anomalies foetales du rein et du tractus urinaire." Doctoral thesis, Universite Libre de Bruxelles, 2006. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210748.

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48

Cunha, Leonardo Provetti. "Correlação entre o eletrorretinograma de padrão reverso, a tomografia de coerência óptica e a perimetria automatizada na detecção da perda neural na atrofia em banda do nervo óptico." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/5/5149/tde-03092010-143434/.

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OBJETIVO: Avaliar a capacidade dos parâmetros do eletrorretinograma de padrão reverso de campo total e hemianópico em diferenciar olhos com atrofia em banda do nervo óptico e, a correlação entre as amplitudes do eletrorretinograma de padrão reverso, a espessura da camada de fibras nervosas da retina e macular obtidas pela tomografia de coerência óptica e a perda de campo visual nestes pacientes. MÉTODOS: Quarenta e um olhos de 41 pacientes com perda de campo visual temporal permanente por compressão do quiasma óptico e 41 controles normais foram submetidos ao eletrorretinograma de padrão reverso de estimulação de campo total e hemianópicos (temporal e nasal), a tomografia de coerência óptica, para avaliação das medidas da espessura da camada de fibras nervosas da retina e macular e, ao exame de campo visual, pela perimetria automatizada padrão. O desvio do normal da sensibilidade dos 18º centrais do campo visual foram expressos em decibéis e unidades 1/Lambert. As comparações foram feitas pelo teste t de Student. A correlação entre os parâmetros do campo visual central, do eletrorretinograma de padrão reverso e da tomografia de coerência óptica foi avaliada pela correlação de Pearson e análise de regressão linear. RESULTADOS: Os valores das amplitudes P50, N95, and P50+N95 do eletrorretinograma de padrão reverso de campo total, e de estimulação hemianópica e os valores das medidas da espessura macular e da camada de fibras nervosas da retina obtidas pela tomografia de coerência óptica foram significativamente menores nos olhos com atrofia em banda do que nos controles (P<0,001). Uma correlação significativa foi encontrada entre a perda de sensibilidade no campo visual central e as amplitudes do eletrorretinograma de padrão reverso de estimulação de campo total e nasal, mas não para o temporal. Uma correlação significativa positiva foi observada entre os parâmetros de perda de sensibilidade no campo visual e a maioria dos parâmetros da espessura da camada de fibras nervosas da retina e macular obtidas pela tomografia de coerência óptica. Nenhuma correlação significativa foi observada entre os parâmetros do eletrorretinograma de padrão reverso e a tomografia de coerência óptica, exceto para amplitude P50+N95 do eletrorretinograma de padrão reverso de estimulação de hemicampo nasal. Uma correlação significativa foi observada entre os parâmetros de espessura macular e da camada de fibras nervosas pela tomografia de coerência óptica, exceto entre a espessura da camada de fibras nervosas no segmento de 30º, correspondente as 9 horas do relógio e os parâmetros maculares. CONCLUSÕES: Os valores das amplitudes do eletrorretinograma de padrão reverso foram eficazes em diferenciar olhos com atrofia em banda do nervo óptico de controles normais. Em pacientes com atrofia em banda do nervo óptico, as amplitudes do eletrorretinograma de padrão reverso e medidas da espessura da camada de fibras nervosas da retina e macular correlacionaram de forma significativa com a perda de campo visual, mas não houve correlação entre eles. O eletrorretinograma de padrão reverso e a tomografia de coerência óptica detectaram a perda neural e ambos são métodos diagnósticos úteis na compreensão da correlação estrutura-função em pacientes com compressão do quiasma óptico<br>PURPOSE: To evaluate the ability of full-field and hemifield pattern electroretinogram parameters to differentiate between healthy eyes and eyes with band atrophy of the optic nerve and also to evaluate the relationship between pattern electroretinogram amplitude, macular and retinal nerve fiber layer thickness by optical coherence tomography, and visual field loss on standard automated perimetry in eyes with BA of optic nerve. METHODS: Forty-one eyes from 41 patients with permanent temporal visual field defects from chiasmal compression and 41 healthy subjects underwent transient fullfield and hemifield (temporal or nasal) stimulation pattern electroretinogram, standard automated perimetry and time domain- optical coherence tomography macular and retinal nerve fiber layer thickness measurements. Comparisons were made using Students t-test. Deviation from normal visual field sensitivity for the central 18° was expressed in dB and 1/Lambert units. Correlations between measurements were verified by Pearsons correlations and linear regression analysis. RESULTS: Full-field P50, N95, and P50+N95 amplitude values were significantly smaller in eyes with band atrophy than in control eyes (P<0.001). Nasal and temporal hemifield pattern electroretinogram studies revealed significant differences in N95 and P50+N95 amplitudes measurements. Pattern electroretinogram and optical coherence tomography measurements were significantly lower in eyes with temporal hemianopia than in normal eyes. A significant correlation was found between visual field sensitivity loss and full-field or nasal, but not temporal, hemifield pattern electroretinogram amplitude. Likewise a significant correlation was found between visual field sensitivity loss and most optical coherence tomography parameters. No significant correlation was observed between optical coherence tomography and pattern electroretinogram parameters, except for nasal hemifield amplitude. A significant correlation was observed between several macular and retinal nerve fiber layer thickness parameters. CONCLUSIONS: Transient pattern electroretinogram amplitude measurements were efficient at differentiating eyes with band atrophy and permanent visual field defects from normal controls. In patients with chiasmal compression, pattern electroretinogram amplitude and optical coherence tomography thickness measurements were significant related to visual field loss, but not to each other. Pattern electroretinogram and optical coherence tomography quantify neuronal loss differently, but both technologies are useful in understanding structure-function relationship in patients with chiasmal compression
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49

Ben, Abdallah Ines. "Sex dimorphism in early Alzheimer’s pathology : brain connectivity with MRI and behavioral analysis in a mouse humanized for APP and MAPT genes." Electronic Thesis or Diss., Strasbourg, 2025. http://www.theses.fr/2025STRAJ008.

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La maladie d’Alzheimer (MA) est une maladie neurodégénérative progressive, qui présente une longue phase préclinique marquée par des changements pathologiques subtils survenant avant l’apparition de symptômes. Les femmes sont plus affectées, présentant un déclin cognitif plus rapide, une plus grande atrophie de l'hippocampe et une pathologie Tau plus étendue que les hommes. Cette thèse explore le dimorphisme sexuel dans la phase préclinique de la MA en utilisant le modèle murin AppNL-F/MAPT double knock-in (dKI). Les évaluations comportementales ont révélé que les souris femelles dKI présentent des déficits de mémoire dans les tâches de reconnaissance d’objet en place et à long terme dès l’âge de 2 mois, tandis que les souris mâles dKI ne présentent des déficits similaires qu’à partir de 4 mois. L’imagerie fonctionnelle a mis en évidence des altérations spécifiques au sexe dans la connectivité du réseau par défaut : les femelles présentaient une hyperconnectivité dans les régions rétrospléniale et entorhinale, tandis que les mâles présentaient une hypoconnectivité dans les voies hippocampo-préfrontales et rétrospléniales, reflétant des vulnérabilités distinctes des réseaux. Ces résultats enrichissent notre compréhension des mécanismes spécifiques au sexe impliqués dans l’apparition de la maladie d'Alzheimer et offrent des pistes pour orienter le développement d’outils diagnostiques précoces<br>Alzheimer’s disease (AD) is a progressive neurodegenerative illness, with a long preclinical phase marked by subtle pathological changes occurring before the onset of overt symptoms. Women are disproportionately affected, more rapid cognitive decline, greater hippocampal atrophy and more extensive Tau pathology than men. This thesis investigates sex dimorphism in preclinical AD using the AppNL-F/MAPT double knock-in (dKI) mouse model. Behavioral assessments revealed that female dKI mice exhibit memory deficits in object-in-place and long- term recognition tasks as early as 2 months, whereas male dKI mice showed similar impairments only by 4 months. Functional imaging highlighted sex-specific alterations in default mode network connectivity: females exhibited hyperconnectivity in retrosplenial and entorhinal regions, while males showed hypoconnectivity in hippocampal-prefrontal and retrosplenial pathways, reflecting distinct network vulnerabilities. These findings advance our understanding of the sex-specific mechanisms underlying AD onset and offers insights that could guide the development of early diagnostic tools
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50

Huchon, Cyrille. "Développement d'un autoquestionnaire pour le diagnostic des algies pelviennes aigües." Phd thesis, Université René Descartes - Paris V, 2012. http://tel.archives-ouvertes.fr/tel-00691369.

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Les algies pelviennes aigues constituent le premier motif de consultation aux urgences gynécologiques. Les étiologies possibles de ces algies pelviennes aigues sont nombreuses et incluent à la fois des affections gynécologiques et non gynécologiques. Certaines de ces affections peuvent, en l'absence de diagnostic précoce et d'un traitement adapté, avoir des conséquences très graves. Dans ce travail, nous avons développé un autoquestionnaire standardisé de manière qualitative dédié aux urgences gynécologiques par des entretiens structurés. Nous avons ensuite construit des modèles de prédiction clinique dédiés (i) au diagnostic de rupture tubaire chez les patientes porteuses de grossesses extra-utérines et (ii) au diagnostic de torsion d'annexe à partir de cet autoquestionnaire. Après avoir défini le concept d'urgence potentiellement à risque en gynécologie, nous avons proposé (iii) un modèle de prédiction clinique de celles-ci basé sur notre autoquestionnaire standardisé. A l'issue du développement de ces modèles, nous avons sélectionné certains items de l'autoquestionnaire standardisé afin d'en proposer une version simplifiée. L'utilisation de nos modèles pour le tri et le diagnostic des patientes aux urgences gynécologiques pourrait permettre d'optimiser la prise en charge des patientes. Dans les groupes à haut risque de pathologie, les patientes pourraient bénéficier d'une prise en charge plus rapide avec une éventuelle diminution de la morbidité secondaire à la pathologie. Pour les patientes classées à bas risque, une désescalade des examens complémentaires et des chirurgies inutiles pourrait aussi permettre une diminution de la morbidité d'origine iatrogène.
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