The endopeptidase activity assay developed for measurement of purified botulinum neurotoxin type A (BoNT/A) in clinical therapeutic preparations has been adopted to provide a specific measure of BoNT/A activity in culture supernatants of proteolytic C. botulinum type A. Electrophoretic studies and inhibition of BoNT/A activity by anti-A antibody confirmed the specificity of the assay. The minimum detection limit was 0.2 MLD50/ml indicating the assay as more sensitive than the standard mouse bioassay or any other in vitro assay available to date. Whilst the assay did not exhibit any cross reactions with non-proteolytic (saccharolytic) clostridia, proteolytic C. botulinum types B and F and C. sporogenes showed some cross reactions. The endopeptidase assay was used to investigate physiological aspects of BoNT/A production by proteolytic C. botulinum type A strain NCTC 7272. Growth studies at 15°C, 25°C and 37°C with strain NCTC 7272 demonstrated that the first appearance of BoNT/A (0.1-1.0 MLD50 ml) occurred during mid-late exponential or early stationary phase of growth. Extracellular BoNT/A formation was not proportional to viable count. Slightly more BoNT/A was detected at 25°C than 37° or 15°C. The results of BoNT/A formation by one of the growth curves at 25°C measured by the endopeptidase assay and mouse bioassays were very similar confirming the specificity of the assay. A simple method was developed to lyre the cells so that BoNT/A formation could be subsequently measured in the endopeptidase assay. The data obtained following lysis of cells and measurement of intracellular BoNT/A showed that both intracellular BoNT/A and total BoNT/A formation is not constitutive but are more closely proportional to viable count than extracellular BoNT/A. Release of BoNT/A from cells was not associated with autolysis. The conversion of BoNT/A from the single-chain to dichain form during growth has been measured. The use of the endopeptidase assay has been also exploited to study BoNT/A formation by this strain within the population of cells. There was only a four-fold difference in BoNT/A production by cells of strain NCTC 7272, and further work in this area is warranted. Attempts were made to use MAPs for the production of monoclonal antibodies to SNAP-25 following cleavage by BoNT/E. Whilst the outcome was unsuccessful, the soundness of the principle was demonstrated

The overall objective of this study was to evaluate the impact of cardiovascular safety concerns on the utilization of the thiazolidinediones (TZDs), pioglitazone and rosiglitazone, and other oral antidiabetic drugs. In May 2007, a meta-analysis was published that found a potential increased risk of myocardial infarction (MI) associated with TZDs, particularly with rosiglitazone. A two-year retrospective study of patients diagnosed with type 2 diabetes (ICD9 250.xx) using prescription and medical databases from the Scott & White Health System (SWHS) was conducted. Patients aged 18 or older who were continuously enrolled with SWHS from 2006 to 2008 and had high adherence (Medication Adherence Ratio ≥80%) for either pioglitazone or rosiglitazone during the pre-safety warning period (May 2006- April 2007) were included. Patients were followed through the post-safety warning period (May 2007 - October 2008) or occurrence of event (discontinuation of index TZD drug). Patients who discontinued their index TZD drug by April 2008 were identified if they had a prescription filled for a new oral antidiabetic drugs (OADs), and followed until October 2008 or occurrence of event (discontinuation of new OAD). Cox proportional hazards models were used to assess the rate of and time to discontinuation of index TZD and new OAD with adjustment of age, gender and Charlson Comorbidity Index (CCI). A total of 531 patients (58 percent male; mean age [SD] = 61 [9.1] years) were included in the final analysis, 255 and 276 patients in the rosiglitazone and pioglitazone groups, respectively. The rate of discontinuation for the pioglitazone and rosiglitazone groups began to separate within 90 days of the index event (meta-analysis published in May 2007). In the pioglitazone group, the rate of discontinuation was significantly lower than in the rosiglitazone group ( HR = 0.56; 95% CI = 0.47, 0.67). A total of 21 patients did not experience discontinuation of their index medication. Among patients receiving a new OAD after discontinuing their index TZD (N = 95 rosiglitazone and N = 33 pioglitazone patients), there was no statistical significant in the rate of discontinuing their new OAD between the rosiglitazone and pioglitazone groups (HR = 0.98; 95% CI = 0.61, 1.59). However, patients who received metformin/sulfonylurea combinations had a lower rate of discontinuation compared to patients who received sulfonylureas (HR = 0.38; 94% CI = 0.21, 0.66). The analysis showed the cardiovascular safety concern of TZDs had a significant impact on the utilization of oral antidiabetic drug utilization. / text

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Measuring process safety performance is a challenge, and the wide variations in understanding, compliance, and implementation of process safety programs increase the challenge. Process safety can be measured in three strata: (1) measurement of process safety elements within facilities; (2) benchmarking of process safety elements among facilities; and (3) use of incident data collection from various sources for industrial safety performance assessment. The methods presently available for measurement of process safety within facilities are deficient because the results are strongly dependent on user judgment. Performance benchmarking among facilities is done within closed groups of organizations. Neither the questionnaires nor the results are available to the public. Many organizations collect data on industrial incidents. These organizations differ from each other in their interests, data collection procedures, definitions, and scope, and each of them analyzes its data to achieve its objectives. However, there have been no attempts to explore the potential of integrating data sources and harnessing these databases for industrial safety performance assessment. In this study we developed models to pursue the measurement of samples of the strata described above. The measurement methodologies employed herein overcome the disadvantages of existing methodologies and increase their capabilities.

The objectives of this study were: (1) to compare lung fibre concentration and dimensions found in two groups of former Quebec chrysotile miners (Asbestos and Thetford-Mines) and, (2) to investigate the relationship between lung-retained mineral fibre concentration and dimension (length, diameter, and aspect ratio) to severity of interstitial lung fibrosis (asbestosis) within these groups. / Lung fibre content was determined for 86 former employees of chrysotile mines and mills in two Quebec mining regions: Thetford-Mines and Asbestos (Jeffrey Mine). Six lung samples were selected for each subject from predetermined intrapulmonary sites. / In summary, the concentrations of tremolite for short (<5 mum) intermediate-length (5--10 mum) and long (>10mum) fibres were 4, 2, and 2 fold higher respectively among workers of Thetford-Mines than those from Asbestos. These differences were statistically significant between the two groups (p < 0.05 for all tremolite size categories). No consistent and biologically important difference was found among fibre dimensions in any of the size categories (p > 0.1 for all fibre types and size categories). These observations suggested that the much higher exposure in Thetford-Mines to asbestos fibres, tremolite fibres being more apparent, is the most plausible factor which may explain the higher incidence of lung diseases among the former miners and millers of Thetford-Mines. / Concentration of short (<5 mum) tremolite fibres was the best predictor of asbestosis severity in both mining groups (r = 0.44, p < 0.01 and r = 0.39 p < 0.01 for Thetford-Mines and Asbestos, respectively). Chrysotile fibre concentration showed a lower correlation with asbestosis severity among subjects from Thetford-Mines (r = 0.28, p < 0.1 and r = 0.39, p < 0.01 and for fibres <5 mum and fibres 5--10 mum respectively). Long (>10 mum) amosite fibre concentrations showed a linear relationship with asbestosis severity in the group of miners and millers from Asbestos (r = 0.5, p < 0.01). Shorter commercial amphibole concentrations did not show this relationship and these fibres were largely absent from the lungs of miners from Thetford-Mines. Concentration of asbestos bodies from lung digests was significantly associated with fibrosis for subjects from Thetford-Mines only (r = 0.3, p = 0.05). (Abstract shortened by UMI.)

Two subject groups, seven PPS (4 males, 3 females) and 15 normal controls (9 females, 6 males) were matched on the basis of age, height and weight and participated in this study. Three repeated measurements were conducted to evaluate the reliability of isokinetic measurement of strength (at 4 velocities) and fatigability (25 reciprocal contractions at 3.14 rads.s$ sp{-1}$). Data from two subsequent test days were used to evaluate the fatigue responses of the PPS subjects while ON or OFF pyridostigmine. Significant strength differences were seen between the two groups, however there was no observed difference in the rate of development of fatigue. Reliability of strength was demonstrated for the knee extensors and flexors of the PPS subjects after three consecutive test days. Fatigability of the knee extensors in PPS subjects could be tested reliably after three test days but more time would be required for reliable performance of the knee flexors. Reliability of strength and fatigability was seen for both the knee extensor and flexors of the normal controls after only two consecutive test days. A beneficial effect of the drug on fatigability was not seen in the three female PPS subjects, but was demonstrated in one male subject. The drug appeared to have a beneficial effect on strength in the remaining three male subjects.

The extant research on the experiences of lesbian/gay, bisexual, and questioning —unsure- (LGBQ) youth shows that they have a lower sense of belonging and safety a tschool, are more likely to be victims of various types of bullying and to skip school, and use drugs and alcohol than their straight peers. Lately, however, a shift in direction towards examining the protective factors, which promote the well being of LGBQ youth, is happening. Extending the emerging research on this shift, the present study investigated the role of supportive adults at school in predicting LGBQ youth sense of safety and belonging. Also, this study examined whether adult support moderated the relationship between sexual orientation victimization and skipping school for LGBQ youth separately. The participants in this study (N = 19,551) were students (grades 8 through 12) enrolled in high schools that took part in a district-wide survey in a large, ethnically and economically diverse urban school district in British Columbia. Results showed that perceptions of adult support played a significant role in predicting the safety and belonging of LGBQ youth. Adult support significantly moderated the relationship between sexual orientation victimization and skipping school for bisexual and questioning youth but not for lesbian/gay youth. The implications, limitations, and directions for future research are discussed in the last section of this thesis.

In order for battery manufacturers to have a sustainable business, the batteries they produce must be as safe as possible. For lithium-ion batteries, reducing the flammability of the electrolyte is considered to be one way to improve safety, which might be achieved by adding flame retardants to the electrolyte. On the other hand, sodium-ion batteries are attracting attention from academic researchers due to the abundance of sodium reserves compared to lithium reserves. However, there are virtually no studies about the safety of sodium-ion batteries. In this thesis, studies of these two issues will be reported. The reactivity of charged/discharged electrode materials for sodium-ion batteries in different solvents and electrolytes at elevated temperature was studied using Accelerating Rate Calorimetry (ARC). Hard carbon was studied as a negative electrode material for sodium-ion batteries. The reactivity of sodium-inserted hard carbon in solvents and electrolytes was investigated. Then, the reactivity of sodium-inserted hard carbon was compared to lithiated graphite. NaCrO2, NaxCoO2 and NaNi0.5Mn0.5O2 were studied as positive electrode materials for sodium-ion batteries. The electrochemical performance of these materials was investigated. The reactivity of charged NaCrO2, NaxCoO2 and NaNi0.5Mn0.5O2 in solvents and electrolytes was studied using ARC. Sodium bis(trifluoromethanesulfonyl)imide (NaTFSI) was studied as an electrolyte salt for sodium-ion batteries. The electrochemical performance of hard carbon and NaCrO2 in NaTFSI/PC electrolyte was studied. The reactivity of sodium-inserted hard carbon and deintercalated NaCrO2 in NaTFSI/PC electrolyte was also investigated. Triphenyl phosphate (TPP) was studied as a flame retardant additive for lithium-ion batteries. Its impact on electrochemical performance of negative electrode materials (petroleum coke and graphite) and positive electrode materials (LiNi1/3Mn1/3Co1/3O2 (NMC) and LiNi0.8Co0.15Al0.05O2 (NCA)) was studied using an automated storage test, symmetric cells and Electrochemical Impedance Spectroscopy (EIS). The reactivity of lithiated graphite, deintercalated NMC and NCA in electrolyte containing TPP was investigated using ARC. Finally, the flammability of electrolytes containing TPP was studied using a Self-Extinguishing Time (SET) test.

Detection of encroachment on pipeline right-of-way is important for pipeline safety. An effective system can provide on-time warning while reducing the probability of false alarms. There are a number of industry and academic developments to tackle this problem. This thesis is the first to study the use of a wireless sensor network for pipeline right-of-way encroachment detection. In the proposed method, each sensor node in the network is responsible for detecting and transmitting vibration signals caused by encroachment activities to a base station (computer center). The base station monitors and analyzes the signals. If an encroachment activity is detected, the base station will send a warning signal. We describe such a platform with hardware configuration and software controls, and the results demonstrate that the platform is able to report our preliminary experiments in detecting digging activities by a tiller in the natural and automotive noise.