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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

The use of salivary biomarkers in the detection of oral squamous cell carcinoma

Matthews, April January 2015 (has links)
Background: Oral squamous cell carcinoma (OSCC) is the 15th most common cancer worldwide but has poor five year survival (50%). Late stage presentation and limitations of early diagnostic techniques are persistent clinical problems. Sixty percent of patients present with advanced stage disease and with the attendant increase in mortality, morbidity and risk of recurrent disease it is particularly burdensome for both patients and health economies. Early diagnosis and treatment of OSCC improves prognosis. There is an opportunity to diagnose OSCC early in patients with oral epithelial dysplasia however currently there is no way of accurately predicting which lesions will undergo malignant transformation. Aberrant methylation of tumour suppressor genes plays a significant role in the biology of early cancer and is detectable in both tumour and saliva. Saliva is a non-invasive method of longitudinal sampling and has potential as a tumour surrogate in disease surveillance programmes. This study aims to compare rates of methylation of a panel of genes in OSCC patients and a normal cohort to establish a threshold by which we could determine future disease testing in a dysplastic population. Methods: Saliva samples were collected from 219 individuals from three diagnostic groups: Normal (defined as no oral malignant or premalignant disease) n=97, OSCC n=62 and dysplasia n=60. For statistical analysis the dysplasia cohort was sub-divided into lesions of low and high risk of malignant transformation based on the histological diagnosis of the index lesion. DNA was extracted and bisulphite treated from 258 saliva samples before duplex quantitative methylation specific PCR (qMSP) assays were performed on all samples to detect the frequency of methylation in saliva of a panel of genes. The five target genes (ADAMTS9, CCNA1, CYGB, P16, TMEFF2) were selected using a candidate approach on the basis of tumour specificity from studies on tumour/normal matched tissue pairs. Clinicopathological data was correlated with the qMSP data and analysed using SPSS v.21 statistical software to look for associations with tumour and survival characteristics. Results: Only 3/97 individuals from the control normal cohort had saliva samples with detectable methylation above the analytical sensitivity of the P16 assay. Methylation of the remaining target genes (ADAMTS9, CCNA1, CYGB, TMEFF2) was not detected in normal saliva at levels above the analytical sensitivity of the qMSP assays. The most significant finding in this study was that methylation of four of the target genes (CCNA1, CYGB, P16, TMEFF2) in saliva, individually and when considered as a panel, was significantly associated with OSCC and as such could aid discrimination between malignant disease and normal saliva samples. Methylation of at least one gene in the panel was discovered in 29/67 of the binned OSCC saliva samples but only 3/97 of normal samples (Fisher’s exact p=0.001). Furthermore methylation of the gene panel is associated with high risk lesions when detected in saliva of patients with premalignant lesions (Fisher’s exact p=0.03). Conclusions: This exploratory data supports the utility of duplex qMSP as a detection method for methylation markers in saliva. The detection of methylation of this gene panel in saliva is significantly more associated with oral malignancy and high risk premalignant lesions than normal and low risk disease. This implies saliva may have merit as a surrogate tissue in an adjunctive role to clinical assessment and biopsy. The assays are specific but have limited sensitivity. However with further work, inclusive of additional genes, this methodology may identify predictive biomarkers that can be introduced into a trial surveillance of premalignant lesions.
2

Three dimensional study to quantify the relationship between facial hard and soft tissue movement as a result of orthognathic surgery

Almukhtar, Anas Mohammed Yousif January 2016 (has links)
Introduction Prediction of soft tissue changes following orthognathic surgery has been frequently attempted in the past decades. It has gradually progressed from the classic “cut and paste” of photographs to the computer assisted 2D surgical prediction planning; and finally, comprehensive 3D surgical planning was introduced to help surgeons and patients to decide on the magnitude and direction of surgical movements as well as the type of surgery to be considered for the correction of facial dysmorphology. A wealth of experience was gained and numerous published literature is available which has augmented the knowledge of facial soft tissue behaviour and helped to improve the ability to closely simulate facial changes following orthognathic surgery. This was particularly noticed following the introduction of the three dimensional imaging into the medical research and clinical applications. Several approaches have been considered to mathematically predict soft tissue changes in three dimensions, following orthognathic surgery. The most common are the Finite element model and Mass tensor Model. These were developed into software packages which are currently used in clinical practice. In general, these methods produce an acceptable level of prediction accuracy of soft tissue changes following orthognathic surgery. Studies, however, have shown a limited prediction accuracy at specific regions of the face, in particular the areas around the lips. Aims The aim of this project is to conduct a comprehensive assessment of hard and soft tissue changes following orthognathic surgery and introduce a new method for prediction of facial soft tissue changes.   Methodology The study was carried out on the pre- and post-operative CBCT images of 100 patients who received their orthognathic surgery treatment at Glasgow dental hospital and school, Glasgow, UK. Three groups of patients were included in the analysis; patients who underwent Le Fort I maxillary advancement surgery; bilateral sagittal split mandibular advancement surgery or bimaxillary advancement surgery. A generic facial mesh was used to standardise the information obtained from individual patient’s facial image and Principal component analysis (PCA) was applied to interpolate the correlations between the skeletal surgical displacement and the resultant soft tissue changes. The identified relationship between hard tissue and soft tissue was then applied on a new set of preoperative 3D facial images and the predicted results were compared to the actual surgical changes measured from their post-operative 3D facial images. A set of validation studies was conducted. To include: • Comparison between voxel based registration and surface registration to analyse changes following orthognathic surgery. The results showed there was no statistically significant difference between the two methods. Voxel based registration, however, showed more reliability as it preserved the link between the soft tissue and skeletal structures of the face during the image registration process. Accordingly, voxel based registration was the method of choice for superimposition of the pre- and post-operative images. The result of this study was published in a refereed journal. • Direct DICOM slice landmarking; a novel technique to quantify the direction and magnitude of skeletal surgical movements. This method represents a new approach to quantify maxillary and mandibular surgical displacement in three dimensions. The technique includes measuring the distance of corresponding landmarks digitized directly on DICOM image slices in relation to three dimensional reference planes. The accuracy of the measurements was assessed against a set of “gold standard” measurements extracted from simulated model surgery. The results confirmed the accuracy of the method within 0.34mm. Therefore, the method was applied in this study. The results of this validation were published in a peer refereed journal. • The use of a generic mesh to assess soft tissue changes using stereophotogrammetry. The generic facial mesh played a major role in the soft tissue dense correspondence analysis. The conformed generic mesh represented the geometrical information of the individual’s facial mesh on which it was conformed (elastically deformed). Therefore, the accuracy of generic mesh conformation is essential to guarantee an accurate replica of the individual facial characteristics. The results showed an acceptable overall mean error of the conformation of generic mesh 1 mm. The results of this study were accepted for publication in peer refereed scientific journal. Skeletal tissue analysis was performed using the validated “Direct DICOM slices landmarking method” while soft tissue analysis was performed using Dense correspondence analysis. The analysis of soft tissue was novel and produced a comprehensive description of facial changes in response to orthognathic surgery. The results were accepted for publication in a refereed scientific Journal. The main soft tissue changes associated with Le Fort I were advancement at the midface region combined with widening of the paranasal, upper lip and nostrils. Minor changes were noticed at the tip of the nose and oral commissures. The main soft tissue changes associated with mandibular advancement surgery were advancement and downward displacement of the chin and lower lip regions, limited widening of the lower lip and slight reversion of the lower lip vermilion combined with minimal backward displacement of the upper lip were recorded. Minimal changes were observed on the oral commissures. The main soft tissue changes associated with bimaxillary advancement surgery were generalized advancement of the middle and lower thirds of the face combined with widening of the paranasal, upper lip and nostrils regions. In Le Fort I cases, the correlation between the changes of the facial soft tissue and the skeletal surgical movements was assessed using PCA. A statistical method known as ’Leave one out cross validation’ was applied on the 30 cases which had Le Fort I osteotomy surgical procedure to effectively utilize the data for the prediction algorithm. The prediction accuracy of soft tissue changes showed a mean error ranging between (0.0006mm±0.582) at the nose region to (-0.0316mm±2.1996) at the various facial regions.
3

Nanopatterning strategies for titanium based medical implants

Greer, Andrew I. M. January 2014 (has links)
This thesis documents the work of Andrew I. M. Greer undertaken for the fulfilment of the requirements for the Degree of Doctor of Philosophy. The project, funded by the EPSRC and MRC, is to develop a nanofabrication processing strategy compatible with titanium based orthopaedic implants. Such a development will facilitate the translation from current and historical in vitro analysis of cell-stimulating nanotopographical cues to in vivo studies upon an implant relevant material. The work presented opens by summarising the social motives and consequences before contextualising the project aims with reference to existing approaches in the field. The thesis progresses through a series of different nanofabrication approaches until an effective strategy satisfying the goals of the project is devised. Thereafter the strategy is explored with its results characterised from a material level through to a biological level. Ultimately the primary goal of the project is realised through the development of novel sol-gel chemistry capable of retaining a nanopattern and transforming into titania, the natural composition at the surface of a titanium based implant. Furthermore, nanofeatures previously too stringent to fabricate for a comprehensive biological study are readily achievable using the documented strategy and fundamental studies have been carried out which indicate that the features concerned are highly effective at up-regulating early indicators of bone formation.

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