The number of patients who have undergone some kind of internal fixation or joint replacement is increasing thanks to the development of technology and orthopaedics. All these patients carry metal implants. Magnetic resonance imaging has an advantage over other imaging methods, due to its superior soft tissue contrast and to its sensitivity in detecting the inflammation which is present at infections and malignancies. However metal implants usually deteriorate the image quality and as a result affect the accuracy of the diagnostic procedure. This is the case when the region of interest is in the proximal vicinity of the implant, or the implant is large enough. A number of MRI sequences have been proposed in order to overcome the artifact that comes from metal implants, more formally known as susceptibility artifact. However the most effective of them, are not widely available. The need for optimization of MR imaging at the presence of metal implants presupposes the development of methods capable of quantifying the artifact under various imaging sequences and conditions. Most artifact quantification techniques proposed until now, are usually based on the visual observation (experienced radiologists) or at image segmentation methods. These segmentation methods, segment the image based on arbitrary selected gray values (thresholds). A more objective and precise quantification method relies on the subtraction of images of a zero artifact replica (test object) from those of the real metal implant. The copy is constructed from material with similar values of magnetic susceptibility with its environment (usually water). The images deriving from the copy if we take in consideration the noise differences, have no susceptibility artifact. In this method artifact is quantified as energy differences between the two images [Kolind S et al, 2004]. Since the acquisition conditions are identical except the presence of susceptibility artifact in the image depicting the real metal object, the energy difference is used to quantify the artifact. While the method quantifies the artifact, giving precise values, it does not inform us for its position in space At this thesis we proposed a new, to our knowledge, method of artifact quantification. It is based in the physical cause of the artifact, which are the gradients of the magnetic field, which derive from the presence of the metal implant. The gradients of the magnetic field create corresponding gradients at the gray scale values of the image. These gradients may be detected if we apply suitable filter which detects the amplitude of the gradient. In this way we detect both regions with signal void (low signal intensity) and signal pill ups (high signal intensity). That means that we do not have to apply two different operators to segment two regions of the artifact with so different signal intensity values. Then the image is thresholded using a fully automated algorithm, proposed by [Li & Lee 1993]. This algorithm is available in image analysis environment ImageJ. At the first part of this thesis there are presented the basic principles of nuclear magnetic imaging image formation. The interaction of the most common materials with the magnetic field is also presented. All these are considered necessary to explain the generation of magnetic susceptibility artifact at the image acquired. The theory beyond the magnetic susceptibility artifact generation is then explained in detail. At the experimental part of this thesis, the proposed algorithm is applied to the imaging of two implants (made of titanium and antimagnetic stainless steel) at the sequences which are most commonly used to musculoskeletal MRI. The proposed algorithm is compared with a variation of the method of the image energy differences proposed by [Kolind Sh, 2004]. This method quantifies the artifact as energy difference of image of the real implant from the image of a replica with zero susceptibility artifact (reference image). In the present thesis the image of lower susceptibility artifact (obtained at higher bandwidth) is considered as reference image. In our case it is assumed that the energy difference among different bandwidth acquisitions is negligible in relation to the susceptibility artifact amplitude. This assumption allows as to use instead of energy differences, the differences in the gray scale values of the image instead. Statistical analysis showed moderate to strong positive correlation between the two methods. Possible reasons of not obtaining strong correlation at all measurements is due to the regions of the image that the proposed algorithm quantifies. By segmenting regions of high gradient, we focus mainly at regions where there is high variation at the gray scale values. However, in many cases nearly homogeneous regions of an image, with little or no alteration in gray scale values, may also be considered as artifact. These areas are not segmented as artifact when the proposed algorithm is applied. More over the assumption of considering negligible the noise contribution between the different acquisitions may be an oversimplification. Nevertheless, the proposed algorithm, is an objective repeatable and observer independent method. Moreover it is capable of determining the boundaries of the artifact in image space. It is not intended to be used as a method of absolute quantification of the susceptibility artifact. It should be used as means of comparison of acquisitions concerning the same sequence. Its combination with an additional algorithmic step, such as one which detects image features may result in a powerful tool of image artifact quantification. This more sophisticated version of this proposed algorithm should be adequate enough to quantify the artifact not only at phantom models but even at the everyday clinical practice. / H εξέλιξη της ιατρικής και ειδικότερα της ορθοπαιδικής έχει κάνει ολοένα και περισσότερο συχνή την ύπαρξη ασθενών που φέρουν μεταλλικά εμφυτεύματα. Η απεικόνιση με μαγνητικό συντονισμό πλεονεκτεί σε σχέση με άλλες απεικονιστικές μεθόδους εξαιτίας της καλύτερης αντίθεσης που προσφέρει στους μαλακούς ιστούς και στην ευαισθησία στην ανάδειξη της φλεγμονής που συνοδεύει τις μολύνσεις και τις κακοήθειες. Η ύπαρξη μεταλλικών εμφυτευμάτων συνήθως υποβαθμίζει την ποιότητα της εικόνας και την καθιστά πολλές φορές μη διαγνωστική, ειδικά αν η περιοχή ενδιαφέροντος είναι κοντά στο μεταλλικό εμφύτευμα ή στην περίπτωση που αυτό είναι αρκετά μεγάλο. Μια σειρά από μεθόδους ή ακόμη και ειδικές ακολουθίες έχει προταθεί κατά καιρούς για να αντιμετωπιστεί η ύπαρξη των τεχνημάτων επιδεκτικότητας, όπως ονομάζονται τα artifact που έχουν σαν αιτία τους τις τοπικές στρεβλώσεις στο μαγνητικό πεδίο εξαιτίας μεταλλικών προθέσεων. Οι πιο αποτελεσματικές από αυτές παραμένουν μη διαθέσιμες για το ευρύ κοινό. Η ανάγκη για βελτιστοποίηση των συνθηκών απεικόνισης κάνει επιτακτική την ανάγκη για ποσοτικοποίηση του artifact στις διαφορετικές συνθήκες λήψεις. Οι τεχνικές ποσοτικοποίησης του artifact που έχουν προταθεί μέχρι σήμερα βασίζονται στην ποιοτική ακτινολογική εκτίμηση (οπτική παρατήρηση) είτε σε μεθόδους τμηματοποίησης της περιοχής εικόνας του artifact που συνήθως στηρίζονται στην επιλογή αυθαίρετων τιμών κατωφλίου τόνων του γκρι. Μια πιο αντικειμενική και ακριβής μέθοδος αφορά στην αφαίρεση εικόνων γεωμετρικού αναλόγου (αντικείμενο ελέγχου- ομοίωμα) του εμφυτεύματος από την εικόνα που απεικονίζει το ίδιο το εμφύτευμα. Το ανάλογο είναι κατασκευασμένο από υλικό με παρόμοια μαγνητική επιδεκτικότητα προς το περιβάλλον του εμφυτεύματος. Η απεικόνιση ενός τέτοιου ομοιώματος, λαμβανομένης υπόψη και της συνεισφοράς του θορύβου, παρουσιάζει μηδενικό artifact επιδεκτικότητας σε σχέση με το πραγματικό εμφύτευμα. Το artifact στην περίπτωση αυτή ποσοτικοποιείται ως διαφορά ενέργειας εικόνας στην περιοχή του περιβάλλοντος υλικού [Kolind S et al,2004]. Η τελευταία αυτή μέθοδος ενώ ποσοτικοποιεί με ακρίβεια το artifact δεν παρέχει πληροφορίες για τη θέση του στο χώρο. Στην παρούσα μεταπτυχιακή εργασία, προτείνεται μία νέα, με βάση τα όσα γνωρίζουμε, μέθοδος ποσοτικοποίησης του artifact. Η μέθοδος αυτή βασίζεται στη γενεσιουργό αιτία του artifact, που είναι οι στρεβλώσεις του μαγνητικού πεδίου από την παρουσία του μεταλλικού αντικειμένου. Οι στρεβλώσεις αυτές εκφράζονται ως βαθμιδώσεις του μαγνητικού πεδίου. Οι βαθμιδώσεις του Μ.Π προκαλούν αντίστοιχες βαθμιδώσεις στην ένταση των τόνων του γκρι στην εικόνα. Αυτές οι βαθμιδώσεις μπορούν να αναδειχθούν αν εφαρμόσουμε κατάλληλο φίλτρο στην εικόνα που ανιχνεύει το μέγεθος/ πλάτος της βαθμίδωσης. Με αυτό τον τρόπο θα ανιχνευτούν τόσο περιοχές με υψηλό όσο και περιοχές με χαμηλό σήμα, απλοποιώντας έτσι τη διαδικασία, αφού δε χρειάζεται να ανιχνευτούν με ξεχωριστό αλγόριθμο περιοχές του artifact με πολύ διαφορετικές τιμές τόνων του γκρι. Στη συνέχεια η εικόνα που προκύπτει κατωφλιώνεται με αυτόματή μέθοδο που έχει προταθεί [Li & Lee 1993] και είναι διαθέσιμη στο περιβάλλον ανάλυσης εικόνας Image J. Στο πρώτο τμήμα της παρούσας εργασίας αναπτύσσονται, συνοπτικά βασικές αρχές του πυρηνικού μαγνητικού συντονισμού και του τρόπου με τον οποίο δημιουργείται η δισδιάστατη εικόνα στο MRI. Ακολουθεί επίσης μια σύντομη περιγραφή του τρόπου με τον οποίο συμπεριφέρονται τα πιο κοινά υλικά όταν βρεθούν εντός του μαγνητικού πεδίου. Όλα αυτά είναι αναγκαία για γίνει κατανοητός ο τρόπος που δημιουργείται το artifact μαγνητικής επιδεκτικότητας στην εικόνα που λαμβάνουμε. Στη συνέχεια αναπτύσσεται με λεπτομέρεια ο μηχανισμός και η φυσική που εμπλέκεται στη δημιουργία των artifact μαγνητικής επιδεκτικότητας. Στο πειραματικό μέρος, εφαρμόζεται ο προτεινόμενος αλγόριθμος σε απεικονίσεις δύο εμφυτευμάτων (τιτανίου και αντιμαγνητικού χάλυβα) στις πιο κοινά χρησιμοποιούμενες ακολουθίες του μυοσκελετικού. Ο προτεινόμενος αλγόριθμος ελέγχεται ως προς την ικανότητα του να ποσοτικοποιεί το artifact με μία παραλλαγή της μεθόδου διαφοράς ενεργειών εικόνων [Kolind Sh,2004]. H μέθοδος αυτή ποσοτικοποιεί το artifact ως διαφορά ενέργειας της εικόνας του πραγματικού εμφυτεύματος από εικόνα γεωμετρικού αναλόγου με μηδενικό artifact (εικόνα αναφοράς). Στην περίπτωση μας χρησιμοποιήσαμε ως εικόνα αναφοράς την εικόνα με το ελάχιστο artifact (η οποία βάσει θεωρίας αντιστοιχεί στη λήψη με το υψηλότερο bandwindth). Επίσης θεωρήσαμε τη διαφορά θορύβου των διαφορετικών λήψεων αμελητέα ως προς τις τιμές έντασης (τόνοι του γκρι) του artifact, ώστε να μπορούμε να αξιοποιήσουμε το πεδίο των τιμών των τόνων του γκρι και όχι αυτό της ενέργειας της εικόνας. Η στατιστική επεξεργασία αναδεικνύει μέτρια ως ισχυρή θετική συσχέτιση των 2 αλγορίθμων. Πιθανοί λόγοι που δεν έχουμε σε όλες τις μετρήσεις ισχυρή ή πολύ ισχυρή συσχέτιση αποδίδονται πρωτίστως στην περιοχή της εικόνας που ποσοτικοποιεί η προτεινόμενη μέθοδος. Τμηματοποιώντας τις βαθμιδώσεις της εικόνας εστιάζουμε σε περιοχές που υπάρχει έντονη μεταβολή των τιμών του γκρι. Παρόλα αυτά το artifact μπορεί κατά περιπτώσεις να περιλαμβάνει και ομοιογενείς περιοχές εικόνας με παραπλήσιες τιμές του γκρι. Αυτές είναι περιοχές που δεν τμηματοποιεί (ανιχνεύει) η προτεινόμενη προσέγγιση. Μια ακόμη αιτία θα μπορούσε να είναι η μη αξιολογήση της συνεισφοράς του θορύβου στις διαφορετικές λήψεις (bandwidths). Η απώλεια τέτοιων περιοχών δεν μειώνει την αξία του αλγορίθμου, αφού αποτελεί μια αντικειμενική μέθοδο, ανεξάρτητη από τον παρατηρητή, επαναλήψιμη και ικανή να οριοθετήσει το artifact στο χώρο. Δεν της επιτρέπει παρόλα αυτά να χρησιμοποιηθεί σαν μέθοδος απόλυτης ποσοτικοποίησης του artifact. Μπορεί να χρησιμοποιηθεί για την πραγματοποίηση συγκρίσεων ιδανικά σε συνθήκες λήψεις που αφορούν την ίδια ακολουθία. Ο συνδυασμός της με ένα επιπλέον αλγοριθμικό βήμα, όπως ένα βήμα που θα ανιχνεύονται χαρακτηριστικά της εικόνας σε συνδυασμό με την οριοθέτηση του artifact που έχει προηγηθεί, μπορεί να δώσει ένα ισχυρό εργαλείο τμηματοποίησης της εικόνας με εφαρμογές που θα μπορούν να επεκταθούν από τη χρήση σε ομοιωμάτων ως εργαλείων για την ποσοτικοποίηση του artifact και στην καθημερινή κλινική πρακτική.

This thesis deals with questions on various applications using soils and sediments as sources of information in archaeological research. Human environmental impact on soils and sediments, in terms of pollution, is a well known phenomenon as the industrialisation intensified during historical times and onwards and has left strong pollutive marks. However, humans have always accumulated or emitted matter and various compounds in connection to their habitats for subsistence, but these earlier traces are not always detectable, depending on soil and sediment state of preservation. Bioessential elements are intimately linked to humans and their dwellings and especially phosphate has been evident in this respect. It was established already in the 1930s, that even Stone Age settlements could be located through elevated phosphate content in extensive soil phosphate mappings. This thesis is a compilation on results from several sites and excavations from the southern to the northern parts of Sweden. There is a wide variety of soil types and chronological setting in the material, from highly acid podzols to calcareous soils, and sediments dated to Younger Dryas to current top soils. Sites from the Mesolithic, Neolithic, Bronze Age, Early and Late Iron Age and Medieval are all represented. Methods that have been implemented are firstly various forms of analysis in regards to soil phosphate, magnetic susceptibility and organic matter. Furthermore, metal and non-metal elements have been considered, as well as lead isotopes. A multiproxy approach is applied in some examples where biological and chemical data is combined to interpret past events. In this thesis there are also five papers presented. The first paper deals with methodological issues concerning multi-element analyses of various soil samples (off-site to feature) from an archaeological excavation. The second paper is about the possibilities that may be used when analysing the soil organic phosphate in relation to prehistoric agriculture. Paper three and fourth are compilations of large scale contract archaeological project. These papers deal with theoretical, methodological and practical issues concerning environmental archaeology in relation to contract archaeology. Studies on landscape development and erosion are among the cases presented. The last paper deals with a late Mesolithic - early Neolithic settlement in Vuollerim, N. Sweden, and spatial dimensions on the human use of settlement (off-site to on-site) and house floors (intra-site), are discussed.

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<p>OVARIAN cancer research focuses on answering important questions related to the disease, determining whether new approaches are feasible to contribute towards improving current treatments or discovering new ones. This study focused on the transcriptional regulation of genes that have been implicated in ovarian cancer, based on the occurrences of single nucleotide polymorphisms (SNPs) within transcription factor binding sites (TFBSs). Through the application of several in silico tools, databases and custom programs, this research aimed to contribute toward the identification of potentially bio-medically important genes or SNPs for pre-diagnosis and subsequent treatment planning of ovarian cancer. A total of 379 candidate genes that have been experimentally associated with ovarian cancer were analyzed. This led to the identification of 121 SNPs that were found to coincide with putative TFBSs potentially influencing a total of 57 transcription factors that would normally bind to these TFBSs. These SNPs with potential phenotypic effect were then evaluated among several population groups, defined by the International HapMap consortium resulting in the identification of three SNPs present in five or more of the eleven population groups that have been sampled.</p>

Landslides, in their various forms, are a common hazard in mountainous terrain, especially in seismically active areas and regions of high rainfall. The West Coast region of New Zealand is dissected by many active faults, experiences frequent earthquakes and in many locations annual rainfall exceeds ten meters. Consequently, landslides are widespread in the region and since European settlement began, have been responsible for 27 deaths, along with frequent damages to road and rail infrastructure, settlements and agricultural land. This study identifies areas that are susceptible to rainfall triggered landslides in the West Coast region. To achieve this, a landslide susceptibility map was produced using bivariate statistics and the analytical hierarchy process. It has an accuracy that predicts 80% of all the landslides in the top 40% of the susceptibility scores on the map. As part of this process, 3221 rainfall triggered landslides and 522 earthquake (or other trigger) triggered landslides have been mapped and digitised into a Geographic Information System. In parallel with this, a descriptive historical catalogue of 1987 landslides has been compiled from the available sources. These new tools provide decision-makers with an enhanced means of managing landslide hazards in the West Coast region. In order to avoid misinterpretation the study has been carried out in compliance with the “Guidelines for landslide susceptibility, hazard and risk zoning for land use planning”, which was published in 2008 by the Joint Technical Committee on Landslides and Engineered Slopes. The tools developed in this thesis represent a fundamental step in land-use planning and set-up of landslide hazard management in the West Coast region.

Nitrogen (N) fertilization is known to influence the susceptibility of many plants to a variety of diseases. In the case of diseases caused by Botrytis cinerea, the role of N fertilization appears to be variable, with high levels either fostering or reducing severity depending on the studies. To test whether this variability could be due to possible differences in the host plants, inoculum pressure or in the behavior of different strains of the pathogen, studies were carried out to investigate the effect of different N fertilization regimes on the susceptibility of tomato and lettuce to six isolates of B. cinerea. Possible epidemiological effects of N fertilization through the sporulation of the pathogen and on the pathogenicity of resulting secondary inoculum were also investigated on tomato. Plants were grown in a soil-less drip-irrigation system. Differential N nutrition ranging from 0.5 to 30 mM NO3- was applied for the last four weeks prior to inoculation on the leaves (lettuce) or on leaf pruning wounds (tomato) and incubation of the plants in conditions conducive to disease development. On the tomato stems, disease onset was delayed and overall severity was lower for all isolates on plants with higher N inputs, regardless of inoculum concentration. However, the rate of stem lesion expansion was differentially affected depending on the strains, decreasing with increasing N fertilization levels for the more aggressive isolates, while increasing for the less aggressive isolates.In contrast with tomato, high N fertilization increased disease severity on lettuce for all isolates tested. On tomato plant tissue, sporulation of B. cinerea decreased significantly with increasing N fertilization up to 15-30 mM NO3- and the pathogenicity of the spores was significantly influenced by the nutritional status of their production substrate. It was highest for spores produced on plants with very low or very high N fertilization (0.5 or 30 mM NO3-) and lowest for those from plants with moderate levels of N fertilization. Plant fertilization also strongly affected the efficacy of two biocontrol agents (Trichoderma atroviride and Microdochium dimerum) to protect pruning wounds of tomato against B. cinerea. The highest levels of protection were obtained with high N fertilization and related to a delay in symptom development on the stems, sometimes associated with a slowdown in lesion expansion. Histological studies showed that the decrease in disease severity at high N fertilization was associated to structural alteration of Botrytis mycelial cells. In the presence of a biocontrol agent, the effect on the pathogen was further associated to vacuolisation, glycogen deposition and mycelial cell death. Hypotheses to explain these results are discussed in light of the possible physiological effects of nitrogen fertilization on nutrient availability for the pathogen in the host tissue and of possible production of defense metabolites by the plant. These results also open new possibilities for including the manipulation of N fertilization as a tool for the integrated protection of vegetable crops

Background: Meat consumption is associated with an elevated risk of colorectal cancer (CRC); exposure to heterocyclic aromatic amines (HAAs), carcinogens produced when meat is cooked at high temperatures, is one hypothesized explanation for this relationship. HAAs form adducts with DNA; left unrepaired, DNA adducts can induce mutations which may initiate and/or promote the development of colorectal adenomas, precursors to the vast majority of CRCs. Along this continuum, genetic differences in the ability to biotransform or metabolize HAAs and repair DNA is postulated to modify the HAA-CRC relationship. Methods: This thesis examined the HAA-CRC relationship in two studies (Phase 1 and 2). In a cross-sectional study of 99 healthy volunteers, Phase 1 investigated the relationship between dietary exposure to HAAs and the levels of bulky DNA adducts in blood leukocytes. In Phase 2, a cross-sectional study examined the relationships between dietary exposures to: a) HAAs and; b) meat mutagenicity, and the prevalence of colorectal adenomas among 342 patients undergoing a screening colonoscopy. Both Phase 1 and 2 examined potential gene-diet interactions between dietary HAAs and genetic factors relevant to the biotransformation of HAAs and DNA repair. Results: In Phase 1, an interaction was observed for dietary HAAs and NAT1 polymorphisms where a positive association between HAA intakes and bulky DNA adduct levels was found among those with the NAT1 slow acetylator genotype, hypothesized to confer a lower ability to biotransform HAAs. In Phase 2, polymorphisms in genes involved in the biotransformation of HAAs (CYP1B1 rs10012 and rs1056827) and DNA repair (XPC rs2228001) were found to determine colorectal adenoma risk. As well, gene-diet interactions were observed for dietary HAAs/meat mutagenicity exposures and polymorphisms in CYP1B1 and XPD (rs13181 and rs1799793). Overall, a higher risk of colorectal adenoma was observed with higher HAA and/or meat mutagenicity exposures among those with polymorphisms which confer a greater activity to biotransform HAAs and/or a lower ability to repair DNA. Conclusion: This research supports the contribution of dietary HAAs and genetic susceptibility to the risk of developing colorectal adenomas and highlighted bulky DNA adduct formation as a potential biologic pathway through which HAAs may influence cancer risk. / Thesis (Ph.D, Community Health & Epidemiology) -- Queen's University, 2014-04-25 11:32:30.392

A human safe, Alhydrogel adjuvanted whole cell Trichomonas vaginalis vaccine was tested for efficacy in a BALB/c mouse model of vaginal infection. Additionally, the systemic and local immune response were measured. Vaccination reduced incidence and increased clearance of infection, and induced both systemic and local humoral immune responses. CD4+ cells were detected in vaginal tissues following intravaginal challenge with T. vaginalis, but were not seen in uninfected mice. CD4+ cells were detected more often, earlier, and in greater numbers in vaccinated vaginal tissues compared to unvaccinated controls. Presence of CD4+ T cells following infection can have significant implications of increasing HIV susceptibility and transmission. These data suggest that the vaccine induces local and systemic immune responses, and confers significantly greater protection against vaginal challenge than unvaccinated vaginal challenge. These data support the potential for a human vaccine against T. vaginalis infection that could also impact the incidence of HIV infections.