BACKGROUND: Multi drug resistant Tuberculosis (MDR-TB) is a serious public health concern in many parts of the world. As per the WHO- 2010 global report on Surveillance and response 3.6% of all incident TB cases globally are multidrug resistant. In this regard, there is an increasing demand for timely, reliable and comprehensive drug susceptibility testing (DST) as MDR-TB surveillance is being geared up. The intent of this analysis is to determine whether there is a need to continue routine confirmatory DST testing at CDC in addition to just sending the isolates for genotyping. Analysis is done by measuring the discordance between the results of laboratory DST at CDC and the local labs drug type, drug testing concentrations, and study sites. METHODS: The data for this analysis was provided by the Tuberculosis Trials Consortium (TBTC), CDC. Data for this analysis was collected over nearly two decades (1993-2011), gathered from 7 clinical trials. Discordance between the local and CDC lab DST results was measured using Kappa statistic. Sensitivity and specificity analysis was done by taking the CDC DST lab results as the gold standard. Discordance levels were calculated by local sites and baseline drug resistance for each antibiotic in each study was measured. RESULTS: Average Kappa values for inter rater agreement for all the studies was 0.6444 whereas the overall level of discordance across all studies is 7.786%. Drug resistance at baseline was highest for Isoniazid and Streptomycin (except Study 23 and 22). CONCLUSION: Though the current results show few DST result discordances between local and CDC labs, it is better to continue to send isolates to the centralized lab (CDC) in view of the worldwide threat of drug resistant TB epidemic, the recommendations of the current literature and the benefits of reliable confirmatory testing services and availability of other molecular diagnostic methods.

Gonorrhea is caused by the human pathogen Neisseria gonorrhoeae. More than 106 million new cases of N. gonorrhoeae infections occur each year worldwide. There is no vaccine available against gonococcal infections and treatment of gonorrhea with antibiotics is the only way to eradicate infection. The high prevalence of antibiotic resistance (AMR) in this microorganism makes the effective treatment of gonococcal infections increasingly problematic. The emergence of AMR, especially to extended spectrum cephalosporins (i.e. cefixime and ceftriaxone) which are the last possibilities for single dose treatment options for gonococcal infections, is a serious concern. Gonorrhea may become an untreatable infection in the near future. Saskatchewan (SK) has one of the highest rates of gonorrhea in Canada. In order to better characterize the gonorrhea epidemic in SK, the objectives of the present research were to determine the prevalence and trends of AMR and emerging AMR mechanisms in N. gonorrhoeae isolates. AMR mechanisms were ascertained for the first time in SK in order to identify genetic causes of resistance. This was completed by determining and analyzing the DNA sequences of various genes - penA, mtrR, porB ponA, gyrA, parC mtrR, 23S rRNA alleles and erm –implicated in gonococcal AMR. The population dynamics of the N. gonorrhoeae isolates in SK was investigated by DNA based molecular methods to determine strain distribution, evolution of AMR phenotypes, and association between strain types (STs) and AMR genotypes and phenotypes. N. gonorrhoeae isolates (n=427) from Saskatchewan (2003-2011) were susceptible to antibiotics now recommended for treatment - cefixime, ceftriaxone and spectinomycin. Over 95% of the isolates tested were also susceptible to penicillin (96%) and ciprofloxacin (95.5%), antibiotics no longer recommended for treatment, and azithromycin (99.4%). Tetracycline resistance was also high (50.1%). N. gonorrhoeae isolates that were resistant to the antibiotics tested and also those isolates with MICs ≥0.003 mg/L to cefixime and ceftriaxone were analyzed (n=146) to determine their resistance mechanisms. This analysis revealed that reduced susceptibility to ceftriaxone and cefixime and resistance to penicillin is mediated by specific mutations in penicillin binding protein 2 (PBP2), in the promoter and dimerization domains of MtrR and porin protein (PorB). Novel mutations and combinations of mutations were noted. Ciprofloxacin resistant N. gonorrhoeae isolates carried double mutations in GyrA (S91F and D95G/N) and a S87R or S88P substitution in ParC. Isolates resistant to azithromycin had specific mutations in all the four alleles of 23S rRNA as well as in the DNA binding domain of MtrR. Most resistance was chromosomally mediated while plasmid-mediated resistance to penicillin (0.93% of penicillin resistant isolates) and tetracycline (3.3%) was low. DNA based strain typing methods such as porB-DNA sequencing, N. gonorrhoeae multi-antigen sequence typing (NG-MAST) and multilocus sequence typing (MLST) showed that the gonococcal population in SK differs appreciably from both other Canadian provinces and from strains reported internationally. MLST analysis, which ascertains the evolution of isolates over time, demonstrated that penicillin and tetracycline resistant isolates in SK evolved through spontaneous mutations in established lineages. Ciprofloxacin and azithromycin resistant N. gonorrhoeae isolates, on the other hand, were introduced into SK from outside the province. Significant associations between particular mutation pattern combinations in resistance determining genes and specific NG-MAST STs were identified e.g. NG-MAST ST 25 was associated with specific combined mutation patterns in PBP2, MtrR and PorB and antibiotic susceptibility; and, NG-MAST ST 3654 was associated with another PBP2/MtrR/PorB mutation pattern, chromosomal resistance to penicillin and tetracycline and elevated MICs to cefixime. This research shows the importance of regional antimicrobial susceptibility monitoring. In the context of SK, this means that local surveillance of gonococcal AMR may be used to develop policies for regional treatment guidelines which promote the prudent use of antimicrobials for treatment, including those antibiotics which may no longer be used in other regions due to higher AMR rates. Further, the significant association between particular AMR mutation pattern combinations and specific STs indicates that AMR might be predicted. These results should assist in the development of non-culture-based tests for the diagnosis of gonococcal AMR similar to nucleic acid amplification tests used to diagnose N. gonorrhoeae infections.

The Saint Lawrence Lowlands in eastern Canada contain extensive deposits of marine soils deposited in post-glacial seas during and following the retreat of the most recent continental glacier. These marine soils include silt and clay deposits known collectively as Champlain clay. When the pore fluid in these marine deposits has changed over time to a lower salinity, the clay can become very sensitive, or demonstrate substantial strength loss after reaching the peak strength with sufficient strain under undrained load conditions. Sensitive clay soils are subject to a peculiar type of very large landslide that typically involves great extents of nearly horizontal ground, usually occurring suddenly and without warning. These landslides tend to be described as “retrogressive” in the literature and practice, implying that they develop as a series of successive small failures that advance rearward until a final stable position is reached. The work of this thesis is organized into four different themes, with an overall objective of understanding the hazard and risk associated with large landslides in sensitive clay to linear infrastructure such as railways. The first theme, documented in Chapter 2, develops a number of spatial relationships between specific physiographic and geologic features and landslide occurrence or absence, as determined through air photo analysis and a review of the literature. The second theme, documented in Chapter 3, presents the construction of a digital database of large landslides in sensitive clay in eastern Canada, for the purposes of studying landslide susceptibility, hazard and risk. The third theme, documented in Chapters 4 and 5, presents and defends a novel mechanical model for development of these large landslides. This model suggests the landslides develop progressively, rather than retrogressively, and the science of fracture mechanics is employed to substantiate the model. The fourth theme, documented in Chapters 6 and 7, synthesizes the findings of the earlier themes and presents a methodology for estimating landslide susceptibility in Champlain clay. That approach is then extended to develop an understanding of the hazard. The concluding chapter extends that work to present an initial appreciation of landslide risk to railways. / Thesis (Ph.D, Geological Sciences & Geological Engineering) -- Queen's University, 2009-04-23 13:22:19.53

Background: Coinfections with multiple types of human papillomavirus (HPV) are a common occurrence among HPV-infected individuals, but the clinical significance and etiology of these infections remain unclear. Though current evidence suggests that women with coinfections have increased HPV exposure (i.e. more sexual partners), it is also hypothesized that these women may represent a subgroup with increased HPV susceptibility, though this has been rarely studied to date. Purpose: The purpose of this project was to examine the occurrence, determinants and dynamics of HPV coinfections in a cohort of university students in order to explore the relationship(s) between coinfections, lifestyle factors and immunological susceptibility. Methods: This project is based on a secondary analysis of data from the McGill-Concordia Cohort, a longitudinal study of the natural history of HPV infection in 621 female university students in Montreal, Quebec. Participants were followed for 2 years at 6-month intervals. At each visit, cervical specimens were collected for cytology and HPV testing, and women completed a questionnaire about lifestyle and risk behaviours. Two definitions of coinfections were used: cumulative coinfection over follow-up and concurrent coinfection at each visit. Kaplan-Meier techniques were used to estimate incidence and duration of coinfections and multiple logistic regression was used to identify determinants of coinfections and associations between coinfections and squamous intraepithelial lesions (SIL). Results: More than half of the cohort became infected with HPV and of those, over 60% acquired multiple HPV types over follow-up. Incidence of coinfections was significantly increased among HPV-infected women at enrollment. The most important determinant of coinfection occurrence was number of sexual partners (both lifetime and new), though some genes of the immune response (HLA-DQB1*06:02, HLA-G*01:01:03 and HLA-G*01:01:05) were also significant predictors. Women with coinfections, particularly those with 4+ HPV types, also had longer infection durations and greatly increased odds of SIL. Conclusions: Women with coinfections acquire new HPV types at an increased rate and have greater HPV persistence and occurrence of SIL, which may indicate immunological susceptibility. HPV coinfections mainly occur due to increased sexual activity but a decreased immune response to the virus may also be involved in a subset of women. / Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2011-04-21 01:04:26.265

No description available.

This thesis has examined the 30km long rail corridor through the Lower Buller Gorge, on the Stillwater Ngakawau Line, between SNL96 and 126km, using a landslide risk management approach. The project area is characterised by high annual rainfall (>2,000mm per year), and steep topography (slopes typically ≥20°) adjacent to the rail corridor. The track formation generally follows the natural contour near the base of the hillslope through the Lower Buller Gorge, and consequently involves many curves but relatively limited cut slopes into adjacent rock outcrops. The distance between the base of adjacent hillslopes and rail is frequently <2m horizontally. A variety of basement and Tertiary lithologies are present, including granite, breccias, indurated sandstone/mudstone, and limestone. The primary focus of this thesis has been on upslope-sourced landsliding onto the rail corridor, and on two short lengths (20m and 450m) that currently have a 25km/hour speed restriction imposed at Whitecliffs and Te Kuha respectively. Rainfall-induced and earthquake-generated landslide triggering mechanisms were examined in detail. A landslide inventory has been compiled to determine the characteristics and distribution of identified slope failures over time, and to establish any correlation with topography and geology. Sixty individual landslide events were identified since the line became fully operational in the 1940s, based on desktop reviews, and field inspections for more recent events. To reflect the presence of small magnitude landslide events, a project-specific logarithmic classification of landslides was adopted from <10m³ (very small volume) to ≥10,000m³ (very large volume). An absence of a higher proportion of ‘very small’ to ‘small’ landslide volumes (<100m³) in the inventory reflects incomplete reporting of these comparatively lower magnitude, but higher frequency, events. The establishment of a robust landslide inventory to document future events, in a consistent and readily accessible format, is required for continued monitoring and review of landslide risk management practices in the Lower Buller Gorge. Combining landslide inventory data and physical characteristics of the project area enabled the development of a qualitative landslide zonation map that assigned ‘high’, ‘high-moderate’, ‘moderate’ and ‘low’ landslide susceptibility classes. The principal area of slope instability above the rail corridor is 22.5km in length between SNL103.5 and 126.0km, associated predominantly with basement lithologies (Tuhua Granite; Hawks Crag Breccia; Greenland Group). The most frequently occurring landslides are shallow, typically less than 3m deep, translational failures triggered in regolith or colluvium materials. Rainfall-induced debris slides and flows are dominant, given the high annual rainfall and associated high frequency of high intensity or long duration rainfall events. Very small to medium landslides (<1,000m³) have the potential to impact the rail corridor with an average frequency of around one every two years, causing damage to infrastructure or affecting rail operations. Very large landslides (≥10,000m³) can be expected every 10 to 20 years based on a limited historical record. The narrow rail corridor and absence of sufficient catch areas above or adjacent to the rail causes continual operational challenges due to upslope-sourced landslide debris, and high susceptibility to slope failures, particularly west of SNL103.50km. Development of a rainfall-threshold for proactive inspection of the rail corridor is recommended, including the establishment of a rain gauge network through the Lower Buller Gorge. Earthquake-generated landslides significantly impacted the rail during the magnitude 7.1 Inangahua earthquake in 1968 and to a much lesser extent during the magnitude 6.1 Westport earthquake in 1991. The rail was not fully constructed through the Lower Buller Gorge at the time of the magnitude 7.8 Buller (Murchison) Earthquake in 1929, which generated widespread landsliding in the Buller and Nelson regions. Earthquake-generated landsliding can be expected through the Lower Buller Gorge from earthquakes of magnitude ≥6, and track inspection is recommended in the event of magnitude 5 or greater earthquakes. Detailed geological characterisation and mapping at Whitecliffs and Te Kuha was conducted, including a LiDAR survey at Whitecliffs that enabled visualisation of the ground surface without the interference of vegetation. The limestone outcrop at Whitecliffs comprises 60-70m high near-vertical cliffs with a well-established talus apron at the base, extending to the rail corridor. Three widely spaced open fractures sets are present at the top of Whitecliffs that propagate into the cliff-face. There has been no detectable movement on selected key fracture sets since monitoring commenced in 1993 and there is no confirmed evidence of large-scale cliff collapse during the 1968 Inangahua earthquake. Whitecliffs is not as susceptible to failure as other slopes inspected in the project area due to structural controls, primarily being the dipping of strata back into the cliff-face and widely space joint sets. Establishment of inspection protocols for earthquake events impacting the area, including real-time monitoring of selected fractures at Whitecliffs is recommended. A 2km-length corridor site model produced for Te Kuha demonstrated ‘high’ landslide susceptibility is not confined to slopes above the existing 450m speed restriction zone. Removal of the speed restrictions at Whitecliffs and Te Kuha can be considered, as the increased exposure time is not considered sufficient justification given the extent of other susceptible areas to landsliding affecting the Lower Buller Gorge rail corridor. The principal conclusion from this thesis project is that there is on-going risk to rail operations predominantly from shallow translational landsliding in regolith-colluvium materials. The majority of these will be generated by long-duration or intense rainfall events. Development of threshold-based methods for effective track management is recommended, including the establishment of a rain gauge network through the Lower Buller Gorge, and landslide inventory database. Site-specific engineering measures could be adopted, such as catch benches or avalanche-type shelters, where justified on a cost-benefit basis.

Ausies uždegimas ne retai pasitaikanti liga porakanopiniams gyvūnams. Dėl racionalaus antimikrobinių vaistų vartojimo, svarbu išskirti ir identifikuoti sukelėjus ir jų jautrumą antimikrobinėms medžiagoms. Mėginiai imti iš dvylikos sveikų kamerūninių ožių, keturių šiaurinių elnių ir keturių lamų ausų landų. Visi gyvūnai yra laikomi Lietuvos zoologijos sode. Išskirti mikroorganizmai (Staphylococcus spp., Streptococcus spp., Escherichia coli, Bacillus spp., Enterococcus spp., Micrococcus spp.) ir nustatytas jų jautrumas antimikrobinėms medžiagoms. Kamerūniniams ožiams iš ausų landų išskirtos mikroorganizmų padermės Bacillus spp. ir Staphylococcus spp. Mikroflora jautriausia antimikrobinėms medžiagoms – amoksicilinui, cefaleksinui ir gentamicinui. Šiauriniams elniams ir lamoms iš ausų landų išskirtos mikroorganizmų padermės Bacillus spp. ir Staphylococcus spp. Mikroflora jautriausia antimikrobinei medžiagai - amoksicilinui. / Otitis is a common disease in artiodactyla animals. Identification the microorganism and begin the antibacterial treatment is important for rational use of antimicrobials. Samples were collected from twelve cameroons goats, four reindeers and four llamas external ear canal. They all are kept in Lithuanian zoo. Staphylococcus spp., Streptococcus spp., Escherichia coli, Bacillus spp., Enterococcus spp., Micrococcus spp. were identified in the samples and set their sensitivity to antimicrobials. In all twelve samples from healthy cameroon goats were identified Bacillus spp. and Staphylococcus spp. Our data showed that healthy cameroon goats sample's microflora were most susceptible to amoxicillini, gentamicini and cephalexini. In all eight samples from healthy llamas anr reinderrs Bacillus spp. and Staphylococcus spp. were identified. Reindeer and llamas external ear canal microflora samples were most susceptible to amoxicillin.

Magistrinio darbo pavadinimas: - “Šunų odos bakterinių ligų sukėlėjų išskyrimas ir jautrumo antimikrobinėms medžiagoms nustatymas““ Autorius: Jogaila Šlekys Magistrinio darbo vadovas: Prof. dr. Jūratė Šiugždaitė Darbo tikslas: Išskirti mikroorganizmus iš šunų odos ir nustatyti jautrumą antimikrobinėms medžiagoms. Rezultatai: Iš 60 tirtų šunų odos mėginių 15 (25 proc.) buvo identifikuoti Staphylococcus aureus mikroorganizmai. 10-tyje mėginių – Streptococcus spp. (16.5 proc.) mikroorganizmai ir 25-se atvejuose (42 proc.) buvo identifikuoti Staphylococcus intermedius mikroorganizmai. 10-tyje mėginių (16,5 proc.) mikroorganizmai neišaugo. Mes nustatėme, kad šunys nuo 1 iki 5 metų amžiaus sirgo daugiausiai (64 proc.). Iš visų tyrime dalyvavusių šunų, sirgusių odos bakterinėmis ligomis , (52 proc.) buvo patelės ir (48 proc.) patinai. Staphylococcus intermedius ir Staphylococcus aureus iškyrimui įtakos turėjo: laikymo sąlygos ir amžius. Sezoniškumas įtakos turėjo Staphylococcus intermedius išskyrimui. Atlikus tyrimus nustatėme, kad Staphylococcus aureus padermės jautriausios buvo ampicilinui (90%) ir cefaleksinui (89%). Staphylococcus intermedius jautriausi buvo cefaleksinui (90 proc.) ir cefovecinui (80 proc.). Streptococcus spp. mikroorganizmai jautriausi buvo tetraciklinui (100 proc.) ir trimetoprimui (100 proc.). Labiausiai mikroorganizmai buvo atsparūs amoksicilinui (100 proc.). Išvados: 1. Atlikus tyrimus nustatėme, kad vyraujantys šunų odos bakterinių ligų sukėlėjai yra... [toliau žr. visą tekstą] / Master final assignment: - “Isolation of dogs bacterial skin disease pathogens and determination of antimicrobial susceptibility“ Author: Jogaila Šlekys Tutor: Prof. dr. Jūratė Šiugždaitė Aim of the study: To evaluate pathogens from canine bacterial skin diseases and determine antimicrobial susceptibility. Results: 15 (25 %) out of 60 cases, where skin smears were taken from domestic animals, pathogenic strains of Staphylococcus aureus were observed, in 10 cases – Streptococcus spp. (16.5%) microorgarnisms and in 25 cases (42%) were determined Staphylococcus intermedius. In 10 samples (16,5%) strains of microorganisms didn‘t occur. We determined, that canine from 1 to 5 years old were mostly affected (64%). We determined that among all of investigated animals morbidity of skin bacterial diseases in females were 52% and in males 48%. Staphylococcus intermedius and Staphylococcus aureus isolation influenced by: canine housing conditions and age. Seasonality affected the Staphylococcus intermedius isolation. During research it was seen that strains of Staphylococcus aureus were most sensitive for Ampicillin (90%) and Cephalexin (89%). Staphylococcus intermedius were most sensitive for Cephalexin (90%) and Cefovecin (80%). Strains of Streptococcus spp. microorganisms mostly showed sensitivity for Tetracycline (100%) and Trimethoprim (100%). Gentamicin was also effective – (75%). Most microorganisms were Amoxicillin resistant (100%). Conclusion: 1. During the research it was... [to full text]

Pathogenesis of prion diseases in animals is associated with the misfolding of the cellular prion protein PrPC to the infectious form, PrPSc. We hypothesized that an animal’s susceptibility to prions is correlated with the propensity of an animal’s PrPC to adopt a β-sheet, PrPSc-like, conformation. We have developed a method which uses circular dichroism (CD) to directly calculate the relative population of PrP molecules that adopt a β-sheet conformation or the ‘β-state’, as a function of denaturant concentration and pH. We find that the PrP from animals that are more susceptible to prion diseases, like hamsters and mice, adopt the β-state more readily than the PrP from rabbits. The X-ray crystal structure of rabbit PrP reveals a helix-capping motif that may lower the propensity to form the β-state. PrP in the β-state contains both monomeric and octameric β-structured species, and possesses cytotoxic properties.

Pathogenesis of prion diseases in animals is associated with the misfolding of the cellular prion protein PrPC to the infectious form, PrPSc. We hypothesized that an animal’s susceptibility to prions is correlated with the propensity of an animal’s PrPC to adopt a β-sheet, PrPSc-like, conformation. We have developed a method which uses circular dichroism (CD) to directly calculate the relative population of PrP molecules that adopt a β-sheet conformation or the ‘β-state’, as a function of denaturant concentration and pH. We find that the PrP from animals that are more susceptible to prion diseases, like hamsters and mice, adopt the β-state more readily than the PrP from rabbits. The X-ray crystal structure of rabbit PrP reveals a helix-capping motif that may lower the propensity to form the β-state. PrP in the β-state contains both monomeric and octameric β-structured species, and possesses cytotoxic properties.