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1
Franco, Iborra Sandra. "Mitochondrial quality control in neurodegenerative diseases: focus on Parkinson’s disease and Huntington’s disease". Doctoral thesis, Universitat Autònoma de Barcelona, 2018. http://hdl.handle.net/10803/565668.
Testo completoAbstract (sommario):
Darrerament s’han produït avanços importants que han contribuït al coneixement dels mecanismes de disfunció cel·lular i mort en la malaltia de Parkinson (MP) i en la malaltia de Huntington (MH). Ambdues malalties són trastorns del moviment que es caracteritzen per la pèrdua específica de neurones dels ganglis basals, les neurones dopaminèrgiques de la substància nigra (SN), en el cas de la MP i les neurones espinoses de l’estriat, en el cas de la MH. Malgrat les diferències, ambdues comparteixen processos patològics comuns com la presència de proteïnes malplegades, l’estrés oxidatiu i disfunció mitocondrial. La mitocòndria és la font d’energia principal en les cèl·lules eucariotes, però també és un orgànul dinàmic relacionat amb una gran quantitat de processos cel·lulars. La disrupció de la homeòstasis mitocondrial i la subseqüent disfunció mitocondrial juguen un paper important en la patofisiologia de les malalties neurodegeneratives. El manteniment de la integritat mitocondrial a través de diferents mecanismes de control és crític per a la superviviència neuronal. Aquesta tesi es centra en l’estudi dels mecanismes de control de qualitat mitocondrial en la MP i la MH, per tal d’entendre millor els mecanismes que duen a la mort cel·lular.
En el primer capítol, he estudiat el transport de proteïnes a la mitocòndria en models in vitro i in vivo de la MP. In vitro, la inhibició del complexe I produeix una alteració del transport de proteïnes a la mitocòndria així com una disminució dels nivells de proteïnes OXPHOS, acumulació de proteïnes agregades i disminució dels nivells de chaperones mitocondrials. Per tal de restablir el transport de proteïnes mitocondrials es van sobreexpressar dos components clau del sistema de translocases: la translocasa de la membrana externa 20 (TOM20) i la translocasa de la membrana interna 23 (TIM23). La sobreexpressió in vitro de TOM20 i TIM23 va restaurar el transport de proteïnes mitocondrials i va alleugerar la disfunció mitocondrial i la mort cel·lular. La inhibició del complexe I en ratolins també dóna lloc a una alteració del transport de proteïnes mitocondrials i produeix neurodegeneració del sistema dopaminèrgic. La sobreexpressió de TIM23 va restaurar parcialment el transport de proteïnes i va protegir lleugerament les neurones dopaminèrgiques de la SN. En canvi, la sobreexpressió de TOM20 va ser incapaç de millorar el transport de proteïnes mitocondrials i, fins i tot, va exacerbar la mort cel·lular. Aquests resultats posen de relleu el paper de la disfunció del transport de proteïnes mitocondrials, en particular de dos dels seus components, en la patogènesis de la MP i suggereixen la necessitat de futurs estudis es centrin en altres elements d’aquest sistema.
En el segon capítol, he estudiat el paper de la proteïna huntingtina en la mitofàgia i com la seva mutació, que dóna lloc a una expansió de glutamines, pot afectar a aquesta funció. Per a tal fi, he treballat en un model in vitro de cèl·lules estriatals ST-Q7 (control) i ST-Q111 (mutant). En condicions fisiològiques, la mitofàgia induïda no es troba mitjançada pel reclutament de parkin als mitocondris despolaritzats. La huntingtina mutada afecta la mitofàgia induïda a través de l’alteració de la seva funció de scaffold en diferents passos del procés de mitofàgia: (i) activació d’ULK1 a través de l’alliberament de mTORC1, (ii) formació del complexe Beclin 1-Vps15,(iii) interacció dels adaptadors de mitofàgia OPTN i NDP52 amb huntingtina i, (iv) amb LC3. Com a resultat, els mitocondris de les cèl·lules ST-Q111 estan més danyats i tenen una respiració mitocondrial deficient. Aquests resultats demostren la presència d’una alteració en la mitofàgia com un mecanisme lligat a la MH. En conclusió, el descobriment de noves dianes mitocondrials en la MP i MH emfatitza el paper important que juga el control de qualitat mitocondrial en la neurodegeneració.In the past years, several important advances have expanded our understanding of the pathways that lead to cell dysfunction and death in Parkinson’s disease (PD) and Huntington’s disease (HD). Both diseases are movement disorders characterized by the loss of a specific subset of neurons within the basal ganglia, dopaminergic neurons in the substantia nigra pars compacta (SNpc), in the case of PD, and medium spiny neurons in the striatum, in the case of HD,. Despite distinct clinical and pathological features, these two neurodegenerative disorders share critical underlying pathogenic mechanisms such as the presence of misfolded and/or aggregated proteins, oxidative stress and mitochondrial anomalies. Mitochondria are the prime energy source in most eukaryotic cells, but these highly dynamic organelles are also involved in a multitude of cellular events. Disruption of mitochondrial homeostasis and the subsequent mitochondrial dysfunction plays a key role in the pathophysiology of neurodegenerative diseases. Therefore, maintenance of mitochondrial integrity through different surveillance mechanisms is critical for neuronal survival. In this thesis I have studied in depth some mitochondrial quality control mechanisms in the context of PD and HD, in order to broaden the knowledge about the pathomechanisms leading to cell death. In the first chapter I have studied mitochondrial protein import in in vitro and in vivo models of PD. In vitro, complex I inhibition, a characteristic pathological hallmark in PD, impaired mitochondrial protein import. This was associated with OXPHOS protein downregulation, accumulation of aggregated proteins inside mitochondria and downregulation of mitochondrial chaperones. Therefore, we aimed to reestablish the mitochondrial protein import by overexpressing two key components of the system: translocase of the outer membrane 20 (TOM20) and translocase of the inner membrane 23 (TIM23). Overexpression of TOM20 and TIM23 in vitro restored protein import into mitochondria and ameliorated mitochondrial dysfunction and cell death. Complex I inhibition also impaired mitochondrial protein import and led to dopaminergic neurodegeneration in vivo. Overexpression of TIM23 partially rescued protein import into mitochondria and slightly protected dopaminergic neurons in the SNpc. On the contrary, TOM20 overexpression did not rescue protein import into mitochondria and exacerbated neurodegeneration in both SNpc and striatum. These results highlight mitochondrial protein import dysfunction and the distinct role of two of their components in the pathogenesis of PD and suggest the need for future studies to target other elements in the system. In the second chapter, I have studied the role of huntingtin in mitophagy and how the polyglutamine expansion present in mutant huntingtin can affect its function. For such, I worked with differentiated striatal ST-Q7 (as control) and ST-Q111 (as mutant) cells, expressing full length huntingtin. In these conditions, induced mitophagy was not mediated by Parkin recruitment into depolarized mitochondria. Mutant huntingtin impaired induced mitophagy by altering wildtype huntingtin scaffolding activity at different steps of mitophagy process: (i) ULK1 activation through its release from the mTORC1, (ii) Beclin1-Vps15 complex formation, (iii) interaction of the mitophagy adapters OPTN and NDP52 with huntingtin and (iv) with LC3. As a result, mitochondria from ST-Q111 cells exhibited increased damage and altered mitochondrial respiration. These results uncover impaired mitophagy as a potential pathological mechanism linked with HD. In conclusion, we have discovered new mitochondrial targets for PD and HD emphasizing the important role that mitochondrial quality control plays in neurodegeneration
2
Mekaru, Sumiko Rachel. "Environmental risk factors in infectious diseases: studies in waterborne disease outbreaks, Ebola, and Lyme disease". Thesis, Boston University, 2013. https://hdl.handle.net/2144/11144.
Testo completoAbstract (sommario):
Thesis (Ph.D.)--Boston UniversityThe resurgence of infectious diseases and global climate change's potential impact on them has refocused public health's attention on the environment's role in infectious disease. The studies in this dissertation utilize the increased availability of satellite image-derived data sets with fine temporal and geographic granularity and the expansion of epidemiologic methods to explore the relationship between the environment and infectious disease in three settings. The first study employed a novel study design and analytic methods to investigate the hypothesis that heavy rainfall is an independent risk factor for waterborne disease outbreaks (WBDOs). We found that a location experiencing a heavy rainfall event had about half the odds of a WBDO two or four weeks later than did a location without a heavy rainfall event. The location-based case-crossover study design utilized in this study may help to expand the research methods available to epidemiologists working in this developing field. The second study employed a location-based case-crossover study design to evaluate standardized differences from historic average of weekly rainfall in locations with a recorded introduction of Ebola into a human. For each 1.0 unit z-score decrease in total rainfall, the odds of an Ebola introduction three weeks later increased by 75%. Given the severity of Ebola outbreaks and the dearth of knowledge about indicators of increased risk, this finding is an important step in advancing our understanding of Ebola ecology. The third study used GIS methods on remote sensing data to estimate the association between peridomestic forest/non-forest interface within 100, 150, 250 meters and Lyme-associated peripheral facial palsy (LAPFP) among pediatric facial palsy patients. After adjustment for sex, age, and socio-economic status, children with the highest level of forest edge in the three radii of analysis had 2.74 (95% CI 1.15, 6.53), 4.58 (1.84, 11.41), and 5.88 (2.11, 16.4) times the odds of LAPFP compared to children with zero forest edge in those radii. This study is the first to examine environmental risk factors for LAPFP. Each of these studies advances the techniques used to investigate environmental risk factors for infectious disease through study design, case definition, data used, or exposure definitions.
3
Pietravalle, SteÌphane. "Modelling weather/disease relationships in winter wheat diseases". Thesis, University of Reading, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.402602.
Testo completo
4
Haslam, Bryan (Bryan Todd). "Learning diseases from data : a disease space odyssey". Thesis, Massachusetts Institute of Technology, 2017. http://hdl.handle.net/1721.1/114002.
Testo completoAbstract (sommario):
Thesis: Ph. D., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2017.Cataloged from PDF version of thesis.
Includes bibliographical references (pages 253-280).
Recent commitments to enhance the use of data for learning in medicine provide the opportunity to apply instruments and abstractions from computational learning theory to systematize learning in medicine. The hope is to accelerate the rate at which we incorporate knowledge and improve healthcare quality. In this thesis, we work to bring further clarity to the ways in which computational learning theory can be applied to update the collective knowledge about diseases. Researchers continually study and learn about the complex nature of the human body. They summarize this knowledge with the best possible set of diseases and how those diseases relate to each other. We draw on computational learning theory to understand and broaden this form of collective learning. This mode of collective learning is regarded as unsupervised learning, as no disease labels are initially available. In unsupervised learning, variance is typically reduced to find an optimal function to organize the data. A significant challenge that remains is how to measure variance in the definition of diseases in a comprehensive way. Variance in the definition of a disease introduces a systematic error in both basic and clinical research. If measured, it would also be possible to use computers to efficiently minimize variance, providing a great opportunity for learning by utilizing medical data. In this thesis, we demonstrate that it is possible to estimate variance in the disease taxonomy, effectively estimating an error bar for the current definitions of diseases. We do so using the history of the disease taxonomy and comparing it with a variety of external data sets that relate diseases to attributes such as symptoms, drugs and genes. We demonstrate that variance can be significant over relatively short time periods. We further present methods for updating the disease taxonomy by reducing variance based on external disease data sets. This makes it possible to automatically incorporate information contained in disease data sets into the disease taxonomy. The approach also makes it possible to use expert information encoded in the taxonomy to systematically transfer knowledge and update other biomedical data sets that are often sparse (e.g. - symptoms associated with diseases). A natural question stemming from these results is how granular does data need to be to make improvements? For instance, is patient-level data necessary to enable learning at the macro level of disease? Or are there strategies to extract information from other kinds of data to alleviate the need for very granular data. We show that detailed, patient-level data is not necessarily needed to extract detailed biological data. We do so by comparing disease relationships learned from clinical trial metadata to disease relationships learned from a detailed genetic database and show we can achieve similar results. This result shows that we can use currently available data and take advantage of computational learning to improve disease learning, which suggests a new avenue to improving patient outcomes. By reducing variance within diseases using data available today, we can quickly update the space of diseases to be more precise. Precise diseases lead to better learning in other areas of medicine and ultimately improved healthcare quality.
by Bryan Haslam.
Ph. D.
5
Guallar-Hoyas, Cristina. "Prospecting for markers of disease in respiratory diseases". Thesis, Loughborough University, 2013. https://dspace.lboro.ac.uk/2134/12415.
Testo completoAbstract (sommario):
Asthma, current detection methods and metabolites proposed as asthma markers are described. The limitation of the disease diagnosis is outlined and metabolomics is introduced as the approach carried out within this research with the potential to measure the group metabolites that characterise the metabolic responses of a biological system to a specific disease. Chemistry underlying breathing, current breath collection and analytical techniques are described as well as detection and data processing technology associated within our research. A work-flow for the collection, analysis and processing of exhaled breath samples in respiratory diseases is described. The non-invasive sampling method allows collection of exhaled breath samples on children and adults without experiencing any discomfort. The analysis of exhaled breath samples using thermal desorption gas chromatography mass spectrometry outlines the use of retention index for the alignment of VOCs retention time shifting over time. This methodology enables the creation of a breath matrix for multivariate analysis data processing where each VOC is defined by retention index and most intense fragments of the mass spectrum. This methodology is tested in two cohorts of participants: paediatric asthma and severe asthmatic participants whose breath profiles are compared against healthy controls and within the two asthmatic phenotypes to prospect the markers that differentiate between the different groups. Eight candidate markers are identified to discriminate between asthmatic children and healthy children and seven markers between asthmatics undergoing therapy and healthy controls. The database from severe and paediatric asthma is compared, establishing seven non-age related markers between the two groups. A new interface is developed for the faster analysis of exhaled breath samples using thermal desorption ion mobility mass spectrometry. The interface front end has been modified and optimised to achieve the best sensitivity and resolution of VOCs in exhaled breath. A preliminary study carried out in a small cohort of volunteers shows the feasibility of the technique for the differentiation of asthmatic and healthy adults.
6
George, Charles Raymond Pax. "Disease Explicated And Disease Defined". Thesis, The University of Sydney, 2005. http://hdl.handle.net/2123/654.
Testo completoAbstract (sommario):
Disease is ubiquitous. Disease afflicts humans. It afflicts animals. It afflicts plants. People refer to disease in their everyday conversation. Newspapers comment upon it. Parliaments enact legislation regarding it. Novelists write about it. Artists depict it. Physicians, veterinary surgeons and agriculturalists seek to combat it. Insurance companies offer reimbursement against it. Anthropologists study it. Philosophers debate its nature, and dictionaries define it. Disease looms large in human consciousness. One might presume that, since disease is so important in daily life, human beings would know exactly what they mean by it. Most people seem to believe instinctively that they understand the nature of disease, and that their ideas about it coincide with other people's ideas. The definition of disease therefore arouses little controversy in everyday conversation. People use the word disease as readily as they use the words spade, or table or nose. They suggest, when they joke that somebody calls a spade a spade, that the nature of the implement used to dig the garden is so obvious that it requires no further definition. Similarly with a table or a nose. They might debate how many legs a table must have, but-regardless of the answer-rarely deny that it is a table; whilst every human must surely know what a nose is. This high level of agreement about so many commonly used terms perhaps creates an assumption that the meaning of disease is equally obvious and requires no further analysis. Is this, however, really the case? Disease is a somewhat less concrete phenomenon than is a spade or a table or a nose. Its existence, most would agree, is incontrovertible, but its nature is less clear. It is something that seems to befall people and animals and plants. It rarely serves any useful purpose. It often carries dire implications. It is something that most of us would prefer not to have, but rarely succeed in avoiding. It commonly comes unannounced and at inconvenient times. It usually causes distress, but not always. It can have a fatal outcome. Some people appear more prone to it that others. It sometimes sweeps through whole populations producing social devastation, but its manifestations vary. Some diseases affect a person's whole body, others merely a part of the body; some affect some parts of the body, others other parts. Some diseases only affect humans, whereas others affect both humans and animals. Some spread from animals to humans, others from humans to humans, and others still do not appear to spread at all. Some diseases affect plants, and few that affect plants seem to affect humans, but some humans can acquire diseases when they come into contact with plants that appear to have no diseases. Any reasonable analysis of the nature of disease must account for all these aspects and many others also. The nature of disease is a topic that has attracted the attention of physicians, scientists and philosophers over millennia. The close association that existed between medicine and philosophy in the classical Egyptian, Palestinian and Greek eras ensured that scholars who flourished in those societies examined the nature of disease. Comparable developments occurred in classical Indian and Chinese civilizations. The natural philosophers of Renaissance and post-Renaissance Europe divided into competing schools of thought over the nature of disease. More recent years have witnessed an enormous flourishing of physicians, pathologists, and agriculturalists who study aspects of disease that relate to their individual disciplines. Most of these researchers have, however, examined ever-narrower aspects of specific diseases-such as manifestations, mechanisms and causes-rather than the generic nature of the phenomenon. Some contemporary philosophers, on the other hand, have become interested in general aspects of the topic. They have proposed a number of novel ideas and reached some stimulating conclusions, although they can hardly yet claim to have reached a consensus. This lack of unanimity presumably implies that the issues involved require closer analysis if a formulation is to emerge that most of them can accept. The object of the present thesis is to undertake such an analysis. It will start by outlining in this introduction the general background to the topic. It will then detail the more noteworthy of previously proposed theories about the nature of this phenomenon, classifying them according to their most prominent components, and assessing their several strengths and weaknesses. It will next discuss the specific philosophical issues of definition, causation, and explication in the biomedical context, before suggesting a comprehensive, but succinct, definition that acknowledges many older views about disease, encompasses current usage, and provides a theoretical base from which to work into the future. It will finally test the strengths and weaknesses of that definition to account for observed phenomena and to accommodate some former definitions.
7
George, Charles Raymond Pax. "Disease Explicated And Disease Defined". University of Sydney. History and Philosophy of Science, 2005. http://hdl.handle.net/2123/654.
Testo completoAbstract (sommario):
Disease is ubiquitous. Disease afflicts humans. It afflicts animals. It afflicts plants. People refer to disease in their everyday conversation. Newspapers comment upon it. Parliaments enact legislation regarding it. Novelists write about it. Artists depict it. Physicians, veterinary surgeons and agriculturalists seek to combat it. Insurance companies offer reimbursement against it. Anthropologists study it. Philosophers debate its nature, and dictionaries define it. Disease looms large in human consciousness. One might presume that, since disease is so important in daily life, human beings would know exactly what they mean by it. Most people seem to believe instinctively that they understand the nature of disease, and that their ideas about it coincide with other people�s ideas. The definition of disease therefore arouses little controversy in everyday conversation. People use the word disease as readily as they use the words spade, or table or nose. They suggest, when they joke that somebody calls a spade a spade, that the nature of the implement used to dig the garden is so obvious that it requires no further definition. Similarly with a table or a nose. They might debate how many legs a table must have, but�regardless of the answer�rarely deny that it is a table; whilst every human must surely know what a nose is. This high level of agreement about so many commonly used terms perhaps creates an assumption that the meaning of disease is equally obvious and requires no further analysis. Is this, however, really the case? Disease is a somewhat less concrete phenomenon than is a spade or a table or a nose. Its existence, most would agree, is incontrovertible, but its nature is less clear. It is something that seems to befall people and animals and plants. It rarely serves any useful purpose. It often carries dire implications. It is something that most of us would prefer not to have, but rarely succeed in avoiding. It commonly comes unannounced and at inconvenient times. It usually causes distress, but not always. It can have a fatal outcome. Some people appear more prone to it that others. It sometimes sweeps through whole populations producing social devastation, but its manifestations vary. Some diseases affect a person�s whole body, others merely a part of the body; some affect some parts of the body, others other parts. Some diseases only affect humans, whereas others affect both humans and animals. Some spread from animals to humans, others from humans to humans, and others still do not appear to spread at all. Some diseases affect plants, and few that affect plants seem to affect humans, but some humans can acquire diseases when they come into contact with plants that appear to have no diseases. Any reasonable analysis of the nature of disease must account for all these aspects and many others also. The nature of disease is a topic that has attracted the attention of physicians, scientists and philosophers over millennia. The close association that existed between medicine and philosophy in the classical Egyptian, Palestinian and Greek eras ensured that scholars who flourished in those societies examined the nature of disease. Comparable developments occurred in classical Indian and Chinese civilizations. The natural philosophers of Renaissance and post-Renaissance Europe divided into competing schools of thought over the nature of disease. More recent years have witnessed an enormous flourishing of physicians, pathologists, and agriculturalists who study aspects of disease that relate to their individual disciplines. Most of these researchers have, however, examined ever-narrower aspects of specific diseases�such as manifestations, mechanisms and causes�rather than the generic nature of the phenomenon. Some contemporary philosophers, on the other hand, have become interested in general aspects of the topic. They have proposed a number of novel ideas and reached some stimulating conclusions, although they can hardly yet claim to have reached a consensus. This lack of unanimity presumably implies that the issues involved require closer analysis if a formulation is to emerge that most of them can accept. The object of the present thesis is to undertake such an analysis. It will start by outlining in this introduction the general background to the topic. It will then detail the more noteworthy of previously proposed theories about the nature of this phenomenon, classifying them according to their most prominent components, and assessing their several strengths and weaknesses. It will next discuss the specific philosophical issues of definition, causation, and explication in the biomedical context, before suggesting a comprehensive, but succinct, definition that acknowledges many older views about disease, encompasses current usage, and provides a theoretical base from which to work into the future. It will finally test the strengths and weaknesses of that definition to account for observed phenomena and to accommodate some former definitions.
8
Mancini, Sabrina. "Assessment of a screening test for MMP-8 activity in the diagnosis of periodontal diseases". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape11/PQDD_0028/MQ40755.pdf.
Testo completo
9
Gu, Mei. "Mitochondrial function in Parkinson's disease and other neurodegenerative diseases". Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.322371.
Testo completo
10
Ullah, Naseem. "Disease modules identification in heterogenous diseases with WGCNA method". Thesis, Högskolan i Skövde, Institutionen för biovetenskap, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-16692.
Testo completoAbstract (sommario):
The widely collected and analyzed genetic data help in understanding the underlying mechanisms of heterogeneous diseases. Cellular components interact in a network fashion where genes are nodes and edges are the interactions. The failure in individual genes lead to dys-regulation of sub-groups of genes which causes a disease phenotype, and this dys-functional region is called a disease module. Disease module identification in complex diseases such as asthma and cancer is a huge challenge. Despite the development of numerous sophisticated methods there is a still no gold standard. In this study we apply different parameter settings to test the performance of a widely used method for disease module detection in multi-omics data called Weighted Gene Co-expression Network Analysis (WGCNA). A systematic approach is used to identify disease modules in asthma and arthritis diseases. The accuracy of obtained modules is validated by a pathway scoring algorithm (PASCAL) and GWAS SNP enrichment. Our results differ between the tested data sets and therefore we cannot conclude with recommendations for an optimal setting that could perform best for multiple data sets using this method.
11
Philips, L. G. "Disease management in chronic kidney disease /". abstract and full text PDF (free order & download UNR users only), 2005. http://0-wwwlib.umi.com.innopac.library.unr.edu/dissertations/fullcit/1430446.
Testo completoAbstract (sommario):
Thesis (M.B.A.)--University of Nevada, Reno, 2005."May, 2005." Includes bibliographical references (leaves 92-97). Online version available on the World Wide Web. Library also has microfilm. Ann Arbor, Mich. : ProQuest Information and Learning Company, [2005]. 1 microfilm reel ; 35 mm.
12
梁欣珮 e Yan-pui Irene Leung. "Potential impact of alzheimer's disease on retina". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B42905059.
Testo completo
13
Hillman, Anne M. "Perceived control in the everyday occupational roles of people with Parkinson's disease and their partners". Connect to full text, 2006. http://hdl.handle.net/2123/1621.
Testo completoAbstract (sommario):
Thesis (Ph. D.)--University of Sydney, 2006.Title from title screen (viewed May 1, 2007). Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the School of Occupation and Leisure Sciences. Includes bibliographical references. Also issued in print.
14
Rodeiro, Carmen Lucia Vidal. "Some issues in disease map modelling and surveillance of diseases". Thesis, University of Aberdeen, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.415553.
Testo completoAbstract (sommario):
The first part of this thesis is dedicated to the study of edge effects in maps of disease. The aim of the analyses is to find out how the estimation of the risk from a disease near boundaries can be affected by the boundary position. The behaviour of a selection of models for disease mapping is evaluated when different edge conditions exist in the data. Disease mapping plays an important role in monitoring the health of a community. Plotting new cases on a map is a frequently used technique for monitoring the spread of infectious diseases and from a statistical point of view it is relevant to consider how statistical methods can be developed or employed to aid the task of surveillance. In the second part of this thesis, methodological and practical issues in developing a rapid response in a spatial surveillance system are discussed. In particular, I review and propose methods for the detection of changes. A simulation study is set up to assess if these methods are good at detecting changes in risk over space and time. An application to a real data set is also given. Surveillance should be performed as quickly as possible but complex Bayesian models require the use of sampling methods to provide estimates of posterior expectations, and these estimates may be computationally expensive to obtain. To aid this, special computational approaches can be considered. One option is to resample the output form initial iterations to provide reweighted estimates as time protocols. This is known a filtration or sequential Monte Carlo. In the third part of this thesis I review the use of sequential Monte Carlo methods (in particular, the Resample-Move algorithm) for dynamic systems, focusing on their use in a surveillance context. This is followed by an application to a real data set where a comparison between the use of McMC methods and the Resample-Move algorithm is carried out.
15
Parton, Matthew James. "Disease-modifying factors in motor neuron disease". Thesis, King's College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.289882.
Testo completo
16
Michell, Andrew William. "Parkinson's disease : α-synuclein and disease markers". Thesis, University of Cambridge, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.613821.
Testo completo
17
Dodd, Will. "Pediatric Respiratory Disease". Digital Commons @ East Tennessee State University, 2017. https://dc.etsu.edu/etsu-works/8938.
Testo completo
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DeMars, Kathleen R., e Nathaniel A. MD Justice. "Pneumonia masking the presentation of incomplete Kawasaki disease". Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/asrf/2019/schedule/76.
Testo completoAbstract (sommario):
Presentation: A 3 month-old male is referred for admission with a 2-day history of fever, having been diagnosed with pneumonia and prescribed a cephalosporin on the previous day. A blood culture obtained at that time is positive for coagulase negative Staphyloccocus.
On exam, he is ill-appearing. He has bilateral conjunctivitis that spares the limbus, non-exudative pharyngitis, and a polymorphic truncal rash. There is no appreciable cervical lymphadenopathy or extremity involvement. A chest x-ray demonstrates a round infiltrate of the left upper lobe, and initial labs reveal a white blood count of 17.5, a C-reactive protein (CRP) of 23.9 mg/dL, and a normal comprehensive metabolic panel. His positive blood culture is deemed a contaminant, and antibiotic coverage for community-acquired pneumonia is given with ampicillin.
Diagnostic evaluation: On day 5 of illness, his fevers persist despite broadened antibiotic coverage. Further work-up has ruled out viral respiratory pathogens and Epstein-Barr virus as a cause of persistent fevers. Incomplete Kawasaki disease is suspected due to continued fevers, the presence of three clinical criteria, and further increase in his CRP. He lacks other supplemental laboratory criteria, so an echocardiogram is obtained that shows mild dilation of the left anterior descending artery (LAD) of indeterminate significance. A repeat echocardiogram 2 days later reveals progressive dilation of left main coronary artery (LMCA), LAD, and right coronary artery (RCA).
Diagnosis: Dilation of the LAD and RCA confirm a diagnosis of incomplete Kawasaki disease. Within 48 hours of treatment with IVIG and high-dose aspirin, the patient is afebrile with resolving symptoms and a declining CRP. He is discharged on the 9th day of illness on low dose aspirin and a cephalosporin to complete an antibiotic course for concurrent pneumonia.
Conclusion & Discussion: This case illustrates the importance of maintaining a high index of suspicion for an incomplete presentation of Kawasaki disease, particularly among infants. The American Heart Association’s guidelines were updated in 2017 to improve recognition of incomplete Kawasaki disease, particularly among infants who are more likely to have an incomplete presentation, abnormalities of the coronary arteries, and a delayed diagnosis. The key to this patient’s diagnosis was the presence of a bilateral conjunctivitis that spared the limbus. A bilateral, non-exudative conjunctivitis that spares the limbus has been recognized as a feature suggestive of Kawasaki disease for the better part of four decades; our review of the literature suggests this feature is highly specific to the diagnosis of Kawasaki disease.
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Phillips, Anne Mairead. "Investigation of the phenotypic and genotypic determinants of disease susceptibility and progression in Crohn's Disease". Thesis, University of Edinburgh, 2011. http://hdl.handle.net/1842/9473.
Testo completoAbstract (sommario):
The inflammatory bowel diseases (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), are chronic inflammatory disorders of the gastrointestinal tract. Their aetiology is not fully understood but is thought to be a combination of the effect of environmental factors in a genetically susceptible person. The work presented is an examination of the phenotypic characteristics of CD in the Scottish population, and an investigation into genetic factors that may influence susceptibility and progression. An IBD cohort from Dundee was recruited (CD=367, UC=265), and extensive phenotypic information collected from these patients together with genomic DNA. Together with the Edinburgh CD cohort already established, the total CD population (n=1155) was examined for time to disease progression (stricturing and/or penetrating disease, according to the Montreal classification) and first resection; a multivariate analysis was performed for factors influencing these outcomes. In this Scottish CD population, the median time to disease progression and first resection was 14.2 years and 8.9 years respectively. The major factor influencing risk of resection and disease progression was disease location, with patients having pure ileal (L1) disease or ileocolonic (L3) disease being more susceptible than those with pure colonic (L2) disease. Compared with L2 disease, the hazards ratios (HR) for disease progression were 4.7 and 2.8, and risk of resection 5.2 and 2.6 for L1 and L3 disease respectively. Disease progression and risk of resection are surrogate markers of disease severity. To try to better understand the determinants of severe disease, a novel score for disease severity was developed and applied to the Dundee CD cohort. This composite score encompassed the variables of medical and surgical management, disease behaviour and location, nutritional status as well as hospitalisations, with a total score that could range from 1 to 16. A score of 7 or more was found to define the 50% of patients with the most severe disease. This cut-off was used to divide patients into less severe and more severe categories; phenotypic and genetic factors were examined for correlation with more severe disease. Genetic factors examined were the 32 most significant CD susceptibility single nucleotide polymorphisms (SNPs) uncovered by recent genome-wide association scans (GWAS). Factors correlated with more severe disease included disease location (L1, odds ratio (OR) 2.20, p=0.0025), age group at diagnosis (p=0.0004) and two CD susceptibility SNPs (rs9286879 and rs17582416; p=0.0085 and p=0.045 respectively). NOD2 was the first IBD susceptibility gene identified. In order to further define pathways involving NOD2, a yeast two-hybrid screen in our laboratory using NOD2 cDNA as the bait had already identified an interaction between NOD2 and UDP-Nacetyl- alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase (GALNT2). This enzyme is involved in O-glycosylation, important in the post translational modification of mucins. A GALNT2 genotype/phenotype analysis on the Edinburgh IBD population was completed, with the Dundee IBD population used as a replication cohort. In the Edinburgh IBD population, the GALNT2 tagging SNP rs7536663 was associated with CD susceptibility (OR 1.38, p=0.0008 vs controls), but replication was not achieved in the Dundee cohort (p=0.469). There was no association of any of the GALNT2 SNPs with UC. The GALNT2/NOD2 interaction was further investigated by completing coimmunoprecipitation between the two genes to characterise the level and type of interaction. An interaction between GALNT2 and NOD2 was confirmed in mammalian cells, with the interaction being at the N-terminal end of the NOD2 protein. GALNT2 expression in a cell line and biopsies was investigated by quantitative polymerase chain reaction and immunohistochemistry respectively. There were no statistically significant changes in GALNT2 or NOD2 mRNA expression in the LS174T cell line after stimulation with specific ligands for NOD2 and GALNT2. GALNT2 protein expression was characterised in intestinal biopsy samples to be predominantly in the lamina propria, with some expression in the enterocytes. To further define the contribution of mucin genes to IBD susceptibility, tagging SNPs across the MUC2, MUC3A and MUC19 genes were genotyped in the Edinburgh IBD cohort and examined for a link with IBD, CD and UC susceptibility, but associations were not found. In view of the strong association with CD susceptibility of a SNP near the MUC19 locus in a recent GWAS, tagging SNPs across the leucine rich repeat kinase-2 (LRRK2) gene, near the MUC19 gene, were also genotyped and examined in the Dundee cohort for an association with IBD, CD and UC susceptibility, but was also negative when corrected for multiple testing. The studies presented allow an improved understanding of the influence of phenotypic characteristics on disease progression, need for surgery and severity in CD. The role of disease location has been determined to be particularly critical, in keeping with other published studies. A detailed examination of the influence of specific genes on disease susceptibility has failed to definitely demonstrate an association between germline variation in GALNT2, MUC2, MUC3A, MUC19 or LRRK2 and IBD, CD or UC susceptibility. An interaction in mammalian cells between NOD2 and GALNT2 has been shown, but further work is required to demonstrate that this is a biologically relevant interaction.
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De, Cruz Glenn. "AIDS ministry a biblical, theological and cultural perspective /". Theological Research Exchange Network (TREN), 1988. http://www.tren.com.
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Miller, Aaron. "Black Band Disease: Elucidating Origins and Disease Mechanisms". FIU Digital Commons, 2012. http://digitalcommons.fiu.edu/etd/558.
Testo completoAbstract (sommario):
Coral diseases were unknown in the scientific community fifty years ago. Since the discovery of a coral disease in 1965, there has been an exponential increase in the number of known coral diseases, as the abundance, prevalence, distribution, and number of host species affected has also significantly increased. Coral diseases are recognized as contributing significantly to the dramatic losses of coral cover on a global basis, particularly in the Caribbean. The apparent sudden emergence of coral diseases suggests that they may be a symptom of an overall trend associated with changing environmental conditions. However, not much evidence has been gathered to address this question. The following studies were designed to build a comprehensive argument to support this hypothesis for one important coral disease – black band disease (BBD).
A meta-analysis of clone libraries identifying the microbial communities associated with BBD reveal important information including that a single cyanobacterial operational taxonomic unit (OTU) was by far the most prevalent OTU in diseased samples, and that the alphaproteobacteria, which include some of the most common bacteria in marine waters, were the most diversely represented. The analysis also showed that samples exhibited regional similarities. An fine and ultrastructural characterization of the disease revealed that the cyanobacteria are prolific borers through the coral skeleton, and that the cyanobacteria penetrate coral tissue, leading to their presence ahead of the main migrating disease band. It was further found that apparently healthy corals exposed to toxins found in BBD, exhibited similar tissue degradation to those infected with BBD. Comparing the disease progression to biofilm formation, it was determined that scouting cyanobacteria may contribute to the migration of the disease through progressive biofilm development over intact coral tissue.
Together, these studies provide significant evidence for the hypothesis that BBD is an opportunistic disease, caused by common environmental bacteria, facilitated by the changing environmental conditions associated with climate change.
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Wang, Juelu. "Selective neurodegeneration in Alzheimer's disease and Parkinson's disease". Thesis, University of British Columbia, 2017. http://hdl.handle.net/2429/63267.
Testo completoAbstract (sommario):
Alzheimer’s disease (AD) and Parkinson’s disease (PD) are featured by cholinergic and dopaminergic neuron loss, respectively. As a unique pathological hallmark of AD, neuritic plaques contain aggregated amyloid β protein (Aβ), generated from amyloid β precursor protein (APP). APP mutations cause familial AD; mutations in the alpha-synuclein (SNCA) and leucine-rich repeat kinase 2 (LRRK2) genes are associated with PD.
Recent studies suggest that the level of LRRK2 affects its toxicity in neurons. Therefore, understanding the mechanisms underlying LRRK2 expression would help to examine its pathogenic effects on PD. However, the features of the LRRK2 promoter remain elusive. In the first project, we cloned and characterized the LRRK2 promoter. There were two functional cis-acting specificity protein 1(Sp1)-responsive elements in its promoter. Our study demonstrates that LRRK2 transcription and translation were facilitated by Sp1 overexpression and blocked by an Sp1 inhibitor in vitro.
The Lewy bodies primarily consist of α-synuclein protein, encoded by SNCA, and SNCAA₅₃T mutation promotes α-synuclein aggregation. The Swedish APP mutation (APPSWE) promotes Aβ generation and AD pathogenesis. However, the mechanisms underlying selective neurodegeneration in AD and PD are still unknown. In the second project, we stably overexpressed wildtype and mutated APP and SNCA genes in cholinergic SN56 and dopaminergic MN9D cells. APPSWE and SNCAA₅₃T mutations enhanced Aβ generation and α-synuclein inclusion formation in SN56 and MN9D cells, respectively. Aβ₄₂ and mutant α-synuclein oligomers caused severe cell death in SN56-APPSWE and MN9D-SNCAA53T cells, respectively. Furthermore, syndecan 3 (SDC3) and fibroblast growth factor receptor like 1 (FGFRL1) genes were identified as two of the differentially expressed genes in APP- and SNCA- related stable cells by microarrays. SDC3 was increased in the cholinergic nucleus of APPSWE knock-in mouse brains, whereas FGFRL1 was elevated in dopaminergic neurons in SNCAA₅₃T transgenic mice. Finally, knockdown of SDC3 and FGFRL1 attenuated oxidative stress-induced cell death in SN56-APPSWE and MN9D-SNCAA₅₃T cells. Overall, these demonstrate that SDC3 and FGFRL1 mediated the specific effects of APPSWE and SNCAA₅₃T on cholinergic and dopaminergic neurodegeneration in AD and PD, respectively. Our study suggests that SDC3 and FGFRL1 could be potential targets to alleviate the selective neurodegeneration in AD and PD.Medicine, Faculty of
Graduate
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Gonsalves, Crystal. "Bimanual coordination in Huntington's disease and Parkinson's disease". Thesis, University of Ottawa (Canada), 2008. http://hdl.handle.net/10393/27588.
Testo completoAbstract (sommario):
Special populations that suffer from Parkinson's disease (PD) and Huntington's disease (HD) display poorer performance in movement and bimanual coordination tasks. Both PD and HD are basal ganglia disorders with neuropathology distinct from one another. The production of internally guided movements is disrupted in PD and HD, therefore utilization of the external pathway may be able to stabilize movements for these groups. The current study examines the effect of auditory cueing for these two populations in timing performance. A total of 10 PD patients, 10 healthy controls (matched for age and gender) and 2 HD patients were examined on a repetitive bimanual finger tapping task. PD patients and healthy controls were asked to perform finger tapping at two different frequencies (1.0 Hz, 2.0 Hz) and two movement types (in-phase, anti-phase). Additionally half of the trials were performed with an external cue (metronome beat), while the other half were not (cue was turned off after 10 metronome heats). Results showed that PD patients were able to effectively use the cue to facilitate bimanual coordination as it was shown that absolute mean timing errors were decreased during the cue trials. PD patients were able to perform both movement types although the more complex mirror asymmetrical anti-phase trials were more difficult to perform. HD patients were not able to achieve the designated fast and slow frequencies that PD and healthy controls performed. The HD patients' movement was highly variable due to tremors and involuntary tics experienced by the patients. Through the examination of raw trajectories and polar plots of phase differences it was concluded that the external cue did not seem to stabilize bimanual coordination for the HD patients.
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Oerton, Erin. "Understanding disease and disease relationships using transcriptomic data". Thesis, University of Cambridge, 2019. https://www.repository.cam.ac.uk/handle/1810/289128.
Testo completoAbstract (sommario):
As the volume of transcriptomic data continues to increase, so too does its potential to deepen our understanding of disease; for example, by revealing gene expression patterns shared between diseases. However, key questions remain around the strength of the transcriptomic signal of disease and the identification of meaningful commonalities between datasets, which are addressed in this thesis as follows. The first chapter, Concordance of Microarray Studies of Parkinson's Disease, examines the agreement between differential expression signatures across 33 studies of Parkinson's disease. Comparison of these studies, which cover a range of microarray platforms, tissues, and disease models, reveals a characteristic pattern of differential expression in the most highly-affected tissues in human patients. Using correlation and clustering analyses to measure the representativeness of different study designs to human disease, the work described acts as a guideline for the comparison of microarray studies in the following chapters. In the next chapter, Using Dysregulated Signalling Paths to Understand Disease, gene expression changes are linked on the human signalling network, enabling identification of network regions dysregulated in disease. Applying this method across a large dataset of 141 common and rare diseases identifies dysregulated processes shared between diverse conditions, which relate to known disease- and drug-sharing-relationships. The final chapter, Understanding and Predicting Disease Relationships Through Similarity Fusion, explores the integration of gene expression with other data types - in this case, ontological, phenotypic, literature co-occurrence, genetic, and drug data - to understand relationships between diseases. A similarity fusion approach is proposed to overcome the differences in data type properties between each space, resulting in the identification of novel disease relationships spanning multiple bioinformatic levels. The similarity of disease relationships between each data type is considered, revealing that relationships in differential expression space are distinct from those in other molecular and clinical spaces. In summary, the work described in this thesis sets out a framework for the comparative analysis of transcriptomic data in disease, including the integration of biological networks and other bioinformatic data types, in order to further our knowledge of diseases and the relationships between them.
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Lopez-Alvarez, Jordi. "Evaluation of early indicators of disease progression in dogs with degenerative mitral valve disease". Thesis, Royal Veterinary College (University of London), 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.669194.
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Kirsch, Florian [Verfasser]. "Economic aspects of disease management programs in chronic diseases / Florian Kirsch". München : Verlag Dr. Hut, 2018. http://d-nb.info/1164293648/34.
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Burge, Susan Mary. "Darier's disease". Thesis, University of Oxford, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.306219.
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Holt, Jim. "Alzheimer’s Disease". Digital Commons @ East Tennessee State University, 2009. https://dc.etsu.edu/etsu-works/6482.
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Holt, Jim. "Heart Disease". Digital Commons @ East Tennessee State University, 2003. https://dc.etsu.edu/etsu-works/6509.
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Williams, Stacey L., e E. Fekete. "Chronic Disease". Digital Commons @ East Tennessee State University, 2012. https://dc.etsu.edu/etsu-works/8145.
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Bernard, Branka. "Huntington's disease". Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2009. http://dx.doi.org/10.18452/15900.
Testo completoAbstract (sommario):
Die Huntington''sche Krankheit (Huntington''s disease, HD) ist eine tödliche neurodegenerative Erkrankung mit einem extensiven Verlust von Neuronen im Striatum. Die Ursache für HD ist eine genetische Mutation, bei der eine CAG-Wiederholungssequenz verlängert wird. Im resultierenden Protein, das Huntingtin (htt) genannt wurde, diese Mutation führt zur Missfaltung und Aggregation von htt. Ich habe untersucht ob die Bildung von htt-Aggregaten die Transkription von Genen dass sie von HD-assoziierten Transkriptionsfaktoren kontrolliert werden, verändert. Zur Untersuchung der Transkription wurden die zu untersuchenden Gene auf cDNA-Mikroarrays aufgebracht und mit RNA, welche aus den Zellen nach der Induktion der Expression des mutierten htt gewonnen wurde, hybridisiert. Es wurden keine systematischen Veränderungen innerhalb der durch spezifische Transkriptionsfaktoren regulierten Gengruppen gefunden. Ich habe auch mehrere mathematische Modelle erstellt, welche die htt-Aggregation und den Zelltod beschreiben. Die Ergebnisse zeigten, dass eine transiente Dynamik im System und die nicht-monotone Reaktion auf Parameteränderungen zu den nicht-intuitiven Ergebnissen bei Behandlungsansätzen, welche die htt-Aggregation beeinflussen, führen könnten. Für den Fall, dass Aggregate die toxische Form von htt sind, zeigten die numerischen Simulationen dass das Einsetzen der Aggregation, welches durch ein Überschießen der Aggregatkonzentration gekennzeichnet ist, am ehesten zum Zelltod führt. Dieses Phänomen wurde "one-shot"-Modell genannt. Es gibt, auch bei HD-Patienten mit gleicher Länge der CAG-Wiederholungssequenz, eine große Varianz des Alters bei Krankheitsausbruch (age of onset, AO). Ich habe ein stochastisches Modell für den neuronalen Zelltod im Striatum entwickelt. Das Modell zeigte, dass ein signifikanter Anteil der nicht erklärbaren Varianz des AO der intrinsischen Dynamik der Neurodegeneration zugeschrieben werden kann.Huntington''s disease (HD) is a fatal neurodegenerative disorder characterized by a progressive neuronal loss in the striatum of HD patients. HD is caused by a CAG repeat expansion which translates into a polyglutamine stretch at the N-terminus of the huntingtin protein (htt). The polyQ stretch induces misfolding, cleavage and aggregation of htt. To test the hypothesis that the sequestration of transcription factors into the htt aggregates causes transcriptional changes observed in HD models, I compiled lists of genes controlled by the transcription factors associated with HD. These genes were spotted on cDNA microarrays that were later hybridized with RNA extracted from cells expressing a mutant htt fragment. In this study, no systematic changes related to a specific transcription factors were observed. Formation and the accumulation of htt aggregates causes neurotoxicity in different HD model systems. To investigate the consequences of therapeutic strategies targeting aggregation, I derived several mathematical models describing htt aggregation and cell death. The results showed that transient dynamics and the non-monotonic response of cell survival to a change of parameter might lead to the non-intuitive outcome of a treatment that targets htt aggregation. Also, the numerical simulations show that if aggregates are toxic, the onset of aggregation, marked by the overshoot in the concentration of aggregates, is the event most likely to kill the cell. This phenomenon was termed a one-shot model. The principal cause of the variability of the age at onset (AO) is the length of the CAG repeat. Still, there is a great variance in the AO even for the same CAG repeat length. To study the variability of the AO, I developed a stochastic model for clustered neuronal death in the HD striatum. The model showed that a significant part of the unexplained variance can be attributed to the intrinsic stochastic dynamics of neurodegeneration.
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Ryan, Philip. "An Investigation Into Novel Molecular Strategies Targeting Neurodegenerative Diseases". Thesis, Griffith University, 2020. http://hdl.handle.net/10072/395102.
Testo completoAbstract (sommario):
Neurodegenerative diseases are characterised by the progressive loss of neuron function and structure. The most prevalent neurodegenerative diseases are hypothesized to be due to the misfolding and accumulation of specific proteins in the brain. Alzheimer’s disease (AD) is suspected to result from the aggregation of amyloid-β (Aβ) or tau proteins, Parkinson’s disease (PD) from the aggregation of α-synuclein (α-syn), and so on for numerous other diseases including Huntington’s disease, amyotrophic lateral sclerosis, and Creutzfeldt-Jakob disease. There are no curative therapies for any of these fatal diseases, only palliative care is available in some cases currently. Research is currently focussed on modulating the aggregation processes common amongst the diseases. Various projects are dedicated to targeting the protein monomers, or small oligomeric assemblies, present at the early stages toward therapy. Modern strategies to target these proteins involve the use of peptide-based agents, effective at selectively binding the proteins through engaging with multiple sites along the protein sequences; and multitarget directed ligands (MTDL), which engage with multiple pathological factors to produce an overall beneficial effect.
Here we set out to investigate various novel chemical scaffolds that we envisaged may prove effective at inhibiting protein aggregation mechanisms in the hopes of identifying new strategies and promising leads. Following review of the literature, compound scaffolds were designed based on existing data and then synthetic chemistry was employed to construct panels of candidate inhibitors. The compounds synthesised were then screened against protein aggregation including Aβ, α-syn and prion formation.
Chapter 2 describes the development of a novel strategy to construct selective glycopeptide-based inhibitors of protein aggregation. This strategy employs the peptide sequences that are reported to recognise the target proteins in their monomeric or oligomeric state and then hinder their aggregation via a disruptive glycoside unit. This component of the project led to the identification of an inhibitor of α-syn aggregation and provided proof-of-concept for the design. The rationale was also used for the construction of Aβ and tau-targeted inhibitors, however evaluation of their effectiveness is ongoing.
Chapter 3 describes the use of the quinazoline scaffold to construct MTDLs designed to be capable of modulating the aggregation of α-syn and the formation of prion proteins. This component of the project led to the identification of a panel of highly potent inhibitors of prion formation in yeast, which are undergoing further evaluation currently, as well as a number of leads that are effective α-syn aggregation inhibitors.
Chapter 4 describes investigation into α-syn oligomerisation modulating analogues of anle138b, a promising candidate undergoing preclinical development. The compounds designed and synthesised were found to be as effective as inhibiting α-syn aggregation in vitro as the preclinical candidate.
Chapter 5 describes attempts at investigating the thiazolone scaffold for use in the design of MTDLs targeting protein aggregation. Unfortunately, this objective of the project was hampered by challenging syntheses and unfavourable solubility profiles, discouraging further commitment to the component of the project.
In summary, a number of novel molecular scaffolds were designed, synthesised and found to be effective modulators of protein aggregation implicated in multiple neurodegenerative diseases. This project has culminated in the identification of promising leads against pathological targets for PD, prionopathy, and AD therapy, as well as contributing to the knowledgebase to stimulate future research efforts.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Pharmacy and Pharmac
Griffith Health
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Rose, Edward Leslie. "Coronary heart disease in patients with peripheral vascular disease". Thesis, University of Oxford, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.305544.
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Archibald, Neil Kenneth. "Visual symptoms in Parkinson's disease and Parkinson's disease dementia". Thesis, University of Newcastle Upon Tyne, 2011. http://hdl.handle.net/10443/1177.
Testo completoAbstract (sommario):
Non-motor symptoms such as dementia and visual hallucinations are key determinants of long-term outcome and quality of life in Parkinson’s disease (PD). Attempting to understand these issues better was the motivation behind this thesis. A major aim of the study was to characterise the visual symptoms experienced by patients with PD and PD dementia, focussing not just on complex visual hallucinations, whose prognostic implications are already well-described, but also on a range of other visual symptoms including illusory misperceptions, sensations of passage and presence and double vision. A major objective was to define key measures of visual exploration strategy during visuocognitive assessment and examine the link between strategy, cognition and visual and motor symptoms. We also set out to examine the utility of retina-specific visual assessment techniques to define the potential role of retinal dysfunction in visual impairment and symptomatology. A major finding of this study was that not all visual symptoms share a common pathophysiological basis. Our results argue in favour of splitting hallucinations into separate phenomenological groups in order to better define causation and predictive value in future longitudinal studies. In addition, exploration strategy on a variety of visual tasks was demonstrated to be significantly less efficient in subjects with perceptual difficulties, providing insight into the interaction between cognition and eye movements in PD. Retinal structure, as assessed by optical coherence tomography, was not significantly altered in PD and our results would caution against the use of this technique as a disease biomarker until more is known about the limitations of this method. Finally, our neurophysiological assessment hints at the retina as the site of diminished visual acuity in PD despite there being no striking differences in central and peripheral retinal responses between control and PD subjects.
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Hunt, Karen Andrea. "Factors regulating inflammation and disease susceptibiity in coeliac disease". Thesis, Queen Mary, University of London, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.497547.
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Cunningham, R. G. C. "Cardiovascular disease in an end stage renal disease population". Thesis, Queen's University Belfast, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.396856.
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James, V. M. "Molecular insights into the disease mechanisms of startle disease". Thesis, University College London (University of London), 2012. http://discovery.ucl.ac.uk/1379645/.
Testo completoAbstract (sommario):
This study describes an in-depth investigation into the pathogenic mechanisms of inherited mutations that lead to disorders of inhibitory glycinergic transmission, primarily the rare human disorder known as startle disease/hyperekplexia. I also investigated mutations causing a similar startle phenotype in cows, mice and zebrafish. Using molecular genetics techniques, I identified pathogenic mutations in the genes that encode for proteins involved in glycinergic neurotransmission, specifically the postsynaptic glycine receptor (GlyR) subunits and the presynaptic glycine transporter GlyT2. Using homology modelling and other computational biology methods, I examined the structural and functional impacts of mutations on protein function, revealing key motifs and amino acids crucial for receptor and transporter activity. Using cDNA cloning and site-directed mutagenesis, I also generated expression constructs for wild-type and mutant proteins that were used in functional tests to measure the impact of pathogenic mutations on glycine receptor and transporter function. For certain animal models of startle disease, I was also able to develop diagnostic PCR tests for pathogenic mutations, which can be used to alleviate further animal suffering by preventing ‘at risk matings’ of carrier animals. Taken together, my findings reveal several new pathogenic mechanisms of GlyR and GlyT2 mutations in startle disease in humans and animals, revealing insights into receptor and transporter function that may be applicable to other neurological disorders.
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McAllister, David Anthony. "Chronic obstructive pulmonary disease, pulmonary function and cardiovascular disease". Thesis, University of Edinburgh, 2011. http://hdl.handle.net/1842/5615.
Testo completoAbstract (sommario):
Cardiovascular disease is common in Chronic Obstructive Pulmonary Disease (COPD), and forced expiratory volume in one second (FEV1) independently predicts cardiovascular morbidity and mortality. Pathological changes in the systemic vasculature have been proposed as potential mechanisms linking COPD to cardiovascular disease, and patients with COPD may be at increased risk of acute myocardial infarction during acute exacerbations. Notwithstanding causation, FEV1 may be a useful prognostic marker in patients undergoing cardiac surgery. This thesis examined these three aspects of cardiovascular co-morbidity in relation to COPD and FEV1. In 2,241 consecutive cardiac surgery patients, FEV1 was associated with length of hospital stay (p<0.001) and mortality (p<0.001) adjusting for age, sex, height, body mass index, socioeconomic status, smoking, cardiovascular risk factors, chronic pulmonary disease, and type/urgency of surgery. In a survey of Scottish Respiratory Consultants there was no consensus regarding the investigation and management of acute coronary syndrome in exacerbation of COPD. In a case-series of 242 patients with exacerbations 2.5% (95% CI 1.0 to 5.6%) had chest pain, raised serum troponin and serial electrocardiogram changes suggestive of acute coronary syndrome. However, over half reported chest pain, while raised troponin was not associated with chest pain or serial ECG changes. Carotid-radial pulse wave velocity (PWV), aortic distensibility, and aortic calcification were measured to assess the relationship of the systemic vasculature to FEV1 and emphysema severity on CT. In adjusted analyses, emphysema was associated with PWV in patients with COPD (p = 0.006) and, in population based samples, with extent of distal aortic calcification (p=0.02) but not with aortic distensibility (p=0.60). This thesis found that FEV1 was associated with mortality and length of hospital stay in patients undergoing cardiac surgery, and that chest pain and raised troponin were common but unrelated in exacerbation of COPD. In the vascular studies distal but not proximal vascular pathology was associated with FEV1, and if COPD is truly related to systemic arterial disease, the distal arterial tree is implicated.
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Carlson, Jodi A. "Procerum root disease physiology and disease interactions with ozone". Diss., Virginia Tech, 1994. http://hdl.handle.net/10919/37445.
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Elitt, Matthew S. "DISEASE MODELING AND THERAPEUTIC DEVELOPMENT FOR PELIZAEUS-MERZBACHER DISEASE". Case Western Reserve University School of Graduate Studies / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=case1536687505814955.
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Ye, Ping. "Autoimmunity in chronic periodontitis". Thesis, The University of Sydney, 2003. http://hdl.handle.net/2123/4256.
Testo completoAbstract (sommario):
Profound perturbation of epithelial structure is a characteristic feature of the immunopatholoical response to bacterial antigens considered to be central in the pathogenesis of the destructive lesion of periodontitis. The pathological basis for the disturbance of epithelial structure is not understood. It was demonstrated that the structural integrity and functional differentiation of the lining epithelium is compromised in relation to inflammatory changes associated with destructive periodontitis. In the pathological lining epithelium of the periodontal pocket there was a marked reduction of epithelial cadherin important in intercellular adhesion, of involucrin, a marker of terminal differentiation, and of the gap junction connexions that form intercellular communication channels. These changes were associated with alterations of filamentous actin expression, collectively indicating profound perturbation of epithelial structure. The data reported support the concept that the ability of the pathological lining epithelium to function as an effective barrier against the ingress of microbial products into the tissues is severely compromised (Ye et al., 2000). In addition, a recent study (Ye et al., 2003) by Western analysis of serum IgG from all 22 patients with chronic periodontitis tested indicated recognition of multiple epithelial components in individual patterns. In contrast, subjects with a healthy periodontium displayed only trace recognition of epithelial antigens. Levels of epithelial-reactive antibodies were significantly correlated with attachment loss as an indication of disease activity. To investigate a possible relationship between the bacterial flora adjacent to the diseased sites and the presence of epithelial-reactive antibodies, subgingival plague samples were taken from deep periodontal pockets and cultured anaerobically. Gram positive bacteria containing antigens potentially cross-reactive with epithelial cells were reproducibly isolated by probing membrane colony lifts with affinity-isolated (epitheial-specific) antibodies. The bacteria were identified as streptococci (S. mitis, S. constellatus and two S. intermedius strains) and Actinomyces (A. georgiae, and A. sp. oral clone) by 16S rDNA sequence homology. Recognition by affinity-isolated antibodies of antigens from the captured organisms was confirmed by Western analysis. Conversely, absorption of affinity-isolated antibodies with bacterial species specifically reduced subsequent recognition of epithelial antigens. To identify the auto-antigens, a human keratinocyte cDNA expression library in Lambda phage was probed using a pooled sera. Groups of responders were detected for CD24 (a recently described adhesion molecule also known as P-selectin ligand), antioxidant protein 2 (a newly recognised member of the thiol-dependment anti-oxidant proteins), lavtate dehydrogenase A, the transcription factor NFAT5, and for three genes encoding novel proteins. Six identified bacteria, especially S intermedius were demonstrated to absorb antibodies reaching with identified auto-antigens in patterns varying between individuals. This evidence indicated that during the course of periodontits, subjects develop increased levels of antibodies to common oral bacteria amongst which are included tissue cross-reactive antigens. Periodontitis could therefore present a risk for the subsequent initiation or exacerbation of a broad spectrum of disease processes including autoimmune, inflammatory, proliferative and degenerative disorders.
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Ye, Ping. "Autoimmunity in chronic periodontitis". University of Sydney, 2003. http://hdl.handle.net/2123/4256.
Testo completoAbstract (sommario):
Doctor of PhilosophyProfound perturbation of epithelial structure is a characteristic feature of the immunopatholoical response to bacterial antigens considered to be central in the pathogenesis of the destructive lesion of periodontitis. The pathological basis for the disturbance of epithelial structure is not understood. It was demonstrated that the structural integrity and functional differentiation of the lining epithelium is compromised in relation to inflammatory changes associated with destructive periodontitis. In the pathological lining epithelium of the periodontal pocket there was a marked reduction of epithelial cadherin important in intercellular adhesion, of involucrin, a marker of terminal differentiation, and of the gap junction connexions that form intercellular communication channels. These changes were associated with alterations of filamentous actin expression, collectively indicating profound perturbation of epithelial structure. The data reported support the concept that the ability of the pathological lining epithelium to function as an effective barrier against the ingress of microbial products into the tissues is severely compromised (Ye et al., 2000). In addition, a recent study (Ye et al., 2003) by Western analysis of serum IgG from all 22 patients with chronic periodontitis tested indicated recognition of multiple epithelial components in individual patterns. In contrast, subjects with a healthy periodontium displayed only trace recognition of epithelial antigens. Levels of epithelial-reactive antibodies were significantly correlated with attachment loss as an indication of disease activity. To investigate a possible relationship between the bacterial flora adjacent to the diseased sites and the presence of epithelial-reactive antibodies, subgingival plague samples were taken from deep periodontal pockets and cultured anaerobically. Gram positive bacteria containing antigens potentially cross-reactive with epithelial cells were reproducibly isolated by probing membrane colony lifts with affinity-isolated (epitheial-specific) antibodies. The bacteria were identified as streptococci (S. mitis, S. constellatus and two S. intermedius strains) and Actinomyces (A. georgiae, and A. sp. oral clone) by 16S rDNA sequence homology. Recognition by affinity-isolated antibodies of antigens from the captured organisms was confirmed by Western analysis. Conversely, absorption of affinity-isolated antibodies with bacterial species specifically reduced subsequent recognition of epithelial antigens. To identify the auto-antigens, a human keratinocyte cDNA expression library in Lambda phage was probed using a pooled sera. Groups of responders were detected for CD24 (a recently described adhesion molecule also known as P-selectin ligand), antioxidant protein 2 (a newly recognised member of the thiol-dependment anti-oxidant proteins), lavtate dehydrogenase A, the transcription factor NFAT5, and for three genes encoding novel proteins. Six identified bacteria, especially S intermedius were demonstrated to absorb antibodies reaching with identified auto-antigens in patterns varying between individuals. This evidence indicated that during the course of periodontits, subjects develop increased levels of antibodies to common oral bacteria amongst which are included tissue cross-reactive antigens. Periodontitis could therefore present a risk for the subsequent initiation or exacerbation of a broad spectrum of disease processes including autoimmune, inflammatory, proliferative and degenerative disorders.
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Ramzan, Naveen, Shimin Zheng, Hemang Panchal, Edward Leinaar, Christian Nwabueze e Timir K. Paul. "Investigating The Association Between Chronic Kidney Disease and Clinical Outcomes". Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/asrf/2019/schedule/21.
Testo completoAbstract (sommario):
Background
Chronic Kidney Disease (CKD) can be described as the loss of the kidney function over time. Symptoms usually develop slowly, and it may not appear in early stages. Lab tests can confirm a CKD diagnosis. The approximate number of incidents per year is more than 200,000 cases, and approximately 30 million people are living with CKD today in the United States. This long-standing disease ultimately leads to renal failure at the end. At this present time, there are no known cures for CKD, and the only treatment available is dialysis. Objectives
The purpose of this study is to determine the association between CKD and further with hemodialysis (HD) and medical condition such as cardiac complications, cardiogenic shock, hemorrhage, anemia, vascular complication, postop respiratory failure, post op infarct hemorrhage, acute renal failure, new temporary pacemaker, new permanent pacemaker, pericardial complications, and death. Study design
The study employed secondary data in a cross-sectional design. Methods
A sample of 106,969 was drawn from the population. The outcome variables were a diagnosis of CKD and/or CKD with HD. The predictor variables were cardiac complications, cardiogenic shock, hemorrhage, anemia, vascular complication, postop respiratory failure, post op infarct hemorrhage, acute renal failure, new temporary pacemaker, new permanent pacemaker, pericardial complications and death. Logistic regression was conducted to analyze the relationship between outcome variable and each independent variable. Variables with a p-value Results
Analysis shows that subjects with cardiac complications were 17% less likely to have CKD as compared to those who did not have cardiac complications (OR: 0.83, 95% CI: 0.78-0.88). CKD patients who had cardiac complications were 18% more likely to have HD than the subjects who did not have cardiac complications (OR: 1.18, 95% CI: 1.01-1.39). Patients with cardiogenic shock were 86% more likely to have CKD than the subjects who did not have cardiogenic shock (OR: 1.86, 95% CI: 1.82-1.91). CKD patients who had cardiogenic shock were also 18% more likely to have HD than the subjects who did not have cardiogenic shock (OR: 1.18, 95% CI: 1.11-1.25). We have similar results if a patient had other conditions. Conclusion
Chronic kidney disease with hemodialysis is significantly associated by the other medical conditions such as cardiac complications cardiogenic shock, hemorrhage, anemia, vascular complication, postop respiratory failure, post op infarct hemorrhage, acute renal failure, new temporary pacemaker, new permanent pacemaker, pericardial complications and death in the United States. Further studies are needed to confirm the results and to understand the prognosis.
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Erdem, Munire Tugba. "Modeling Diseases With Multiple Disease Characteristics: Comparison Of Models And Estimation Methods". Master's thesis, METU, 2011. http://etd.lib.metu.edu.tr/upload/12613531/index.pdf.
Testo completoAbstract (sommario):
Epidemiological data with disease characteristic information can be modelled in several ways. One way is taking each disease characteristic as a response and constructing binary or polytomous logistic regression model. Second way is using a new response which consists of disease subtypes created by cross-classification of disease characteristic levels, and then constructing polytomous logistic regression model. The former may be disadvantageous since any possible covariation between disease characteristics is neglected, whereas the latter can capture that covariation behaviour. However, cross-classifying the characteristic levels increases the number of categories of response, so that dimensionality problem in parameter space may occur in classical polytomous logistic regression model. A two staged polytomous logistic regression model overcomes that dimensionality problem. In this thesis, study is progressen in two main directions: simulation study and data analysis parts. In simulation study, models that capture the covariation behaviour are compared in terms of the response model parameter estimators. That is, performances of the maximum likelihood estimation (MLE) approach to classical polytomous logistic regression, Bayesian estimation approach to classical polytomous logistic regression and pseudo-conditional likelihood (PCL) estimation approach to two stage polytomous logistic regression are compared in terms of bias and variation of estimators. Results of the simulation study revealed that for small sized sample and small number of disease subtypes, PCL outperforms in terms of bias and variance. For medium scaled size of total disease subtypes situation when sample size is small, PCL performs better than MLE, however when the sample size gets larger MLE has better performance in terms of standard errors of estimates. In addition, sampling variance of PCL estimators of two stage model converges to asymptotic variance faster than the ML estimators of classical polytomous logistic regression model. In data analysis, etiologic heterogeneity in breast cancer subtypes of Turkish female cancer patients is investigated, and the superiority of the two stage polytomous logistic regression model over the classical polytomous logistic model with disease subtypes is represented in terms of the interpretation of parameters and convenience in hypothesis testing.
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Chochó, Karen S. "Hispanic migrants and cross-border disease control of Arizona's vaccine preventable diseases". restricted, 2008. http://etd.gsu.edu/theses/available/etd-04222008-151047/.
Testo completoAbstract (sommario):
Thesis (M.Ph.)--Georgia State University, 2008.Title from file title page. Richard Rothenberg, committee chair; Russ Toal, Karen E. Gieseker, committee members. Electronic text (135 p. : col. ill.) : digital, PDF file. Description based on contents viewed August 12, 2008. Includes bibliographical references (p. 127-135).
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Chocho, Karen. "Hispanic Migrants and Cross-border Disease Control of Arizona's Vaccine Preventable Diseases". Digital Archive @ GSU, 2008. http://digitalarchive.gsu.edu/iph_theses/35.
Testo completoAbstract (sommario):
BACKGROUND: According to the Centers for Disease Control and Prevention and the National Immunization Program, there is an increase in the re-emergence of past diseases. Even with mandatory vaccination practices in the United States, there are still a number of cases of vaccine-preventable diseases (VPDs) reported yearly. It is speculated that the re-emergence of VPDs is in part due to the increase in international travel as well as the influx of immigrants. One particular group of interest includes the Hispanic migrants coming from Central and South America where some of these diseases are endemic. OBJECTIVE: The purpose of this paper is to determine the extent of VPD cases in the border state of Arizona that may be attributed to Hispanic migrant influx using data from the MMWR: Summary of Notifiable Diseases reports for the United States and the ADHS data from all Arizona counties. RESULTS: Since 1995, rates of hepatitis B and pertussis have been increasing in Arizona and have become higher for non-Hispanics than Hispanics. In 2005, hepatitis B rates were 1.53* for the United States and 7.31* for Arizona; pertussis rates were 8.72* for the United States and 21.60* for Arizona. CONCLUSION: The results of this study's analysis show the need to improve immunization efforts within the non-Hispanic populations in all Arizona counties. (*Per 100,000 population)
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Yassin, Khaled. "Unravelling the mystery of liver diseases in Egypt : the burden of disease /". Lage : Jacobs, 2001. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=009222709&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.
Testo completo
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Adanyeguh, Isaac Mawusi. "Biomarkers Identification and Disease Modeling using Multimodal Neuroimaging Approaches in Polyglutamine Diseases". Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066279/document.
Testo completoAbstract (sommario):
Les maladies par expansion de polyglutamines sont des maladies neurodégénératives dues à l’expansion du trinucléotide cytosine-adénine-guanine (CAG) dans les gènes correspondants codant pour une expansion d’homopolymère de glutamine dans les protéines mutées. Ce projet concerne les formes les plus courantes qui sont la maladie de Huntington (MH) et les ataxies spinocérébelleuses (SCA) types 1, 2, 3 et 7. Ce sont des maladies autosomiques dominantes, responsables de troubles graves de la motricité partageant des voies physiopathologiques communes, avec un effet notable sur la dysfonction métabolique. La disponibilité des tests génétiques et le fait que la plupart du temps la maladie débute à l’âge adulte offre la possibilité d’une intervention thérapeutique avant l’apparition de symptômes. Toutefois, les échelles cliniques ne sont pas assez sensibles et ne peuvent effectivement être utilisés pour évaluer les personnes au stade présymptomatique de la maladie. Les techniques d’imagerie par résonance magnétique (IRM) et de spectroscopie (SRM) sont des approches non invasives qui permettent de recueillir des informations pertinentes et sensibles. Ainsi, dans ce travail, nous présentons une combinaison de différentes techniques d’IRM et SRM afin d’identifier de robustes biomarqueurs de la MH et des SCA. Nous présentons aussi des approches thérapeutiques prometteuses dans la MH. De la même manière, nous voulons démontrer que des biomarqueurs d’imagerie sont plus sensibles que des échelles cliniques. Pour conclure, nous combinons des données multimodales – volumétrie, SRM, métabolomique et lipidomique – à partir de SCA dans un modèle qui explique mieux la pathologieMutations in different gene loci that lead to the encoding of the unstable and expanded glutamine-encoding cytosine-adenine-guanine (CAG) repeats results in the group of diseases known as the polyglutamine diseases. This project focuses on the most common forms which are Huntington disease (HD) and spinocerebellar ataxia (SCA) types 1, 2, 3 and 7. These are autosomal dominant diseases responsible for severe movement disorders and are thought to share common pathophysiological pathways with a major emphasis on metabolic dysfunction. The availability of genetic testing and their predominantly adult onset opens a window for therapeutic intervention before symptoms onset. However, current clinical scales are not sensitive and cannot effectively be used to evaluate individuals at the presymptomatic stage of the diseases. This prompts the need for biomarkers that are sensitive to macroscopic and microscopic changes that may occur prior to disease onset. Magnetic resonance imaging (MRI) and spectroscopy (MRS) techniques present non-invasive approaches to extract pertinent information that otherwise would not be possible with clinical scales. In this work therefore, we present a combination of different MRI and MRS techniques to identify robust biomarkers in HD and SCA. We also present therapeutic approaches that hold promise in HD. Likewise, we show that imaging biomarkers have higher effect sizes than clinical scales. Finally, we combine multimodal data – volumetry, MRS, metabolomics and lipidomic – from SCA into a model that best explains the pathology
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Gadd, Malin. "Cardiovascular diseases in immigrants in Sweden /". Stockholm : Neurotec, Center for family and community medicine, Karolinska institutet, 2006. http://diss.kib.ki.se/2006/91-7140-627-1/.
Testo completo
50
Srinivasan, BadriNarayanan. "Unsupervised learning to cluster the disease stages in parkinson's disease". Thesis, Högskolan Dalarna, Datateknik, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:du-5499.
Testo completoAbstract (sommario):
Parkinson's disease (PD) is the second most common neurodegenerative disorder (after Alzheimer's disease) and directly affects upto 5 million people worldwide. The stages (Hoehn and Yaar) of disease has been predicted by many methods which will be helpful for the doctors to give the dosage according to it. So these methods were brought up based on the data set which includes about seventy patients at nine clinics in Sweden. The purpose of the work is to analyze unsupervised technique with supervised neural network techniques in order to make sure the collected data sets are reliable to make decisions. The data which is available was preprocessed before calculating the features of it. One of the complex and efficient feature called wavelets has been calculated to present the data set to the network. The dimension of the final feature set has been reduced using principle component analysis. For unsupervised learning k-means gives the closer result around 76% while comparing with supervised techniques. Back propagation and J4 has been used as supervised model to classify the stages of Parkinson's disease where back propagation gives the variance percentage of 76-82%. The results of both these models have been analyzed. This proves that the data which are collected are reliable to predict the disease stages in Parkinson's disease.