Abstract Safety assessment relating to the presence of impurities, residual materials and contaminants in vaccines is a focus area of research at the United States Food and Drug Administration (FDA). Sponsors who submit Investigational New Drug (IND) applications for new vaccine products must report the results of safety assessments to the Division of Vaccines and Related Products Applications (DVRPA). Scientifically defining thresholds of toxicological concern (TTCs) as they apply to vaccine constituents will provide a useful aid to the sponsors and public regarding safety assessments of compounds for which there is little or no toxicity data. TTCs are mathematically modeled and extrapolated levels, below which adverse human health effects are not expected to occur (Kroes, 2004). In this project, we accessed DVRPA's submission databases and open source data to yield an initial chemical test set. Using INCHEM, RepDose, RTECS and TOXNET, we gathered LD50 and TDLo data. Using a structure-based decision tree, provided in the ToxTree software package, (3) different algorithms (The Cramer extended, the In vivo rodent micronucleus assay, and the Benigni-Bossa rule base for carcinogenicity by ISS) were applied to assign the initial test set (n= 197) of chemicals into structural families based on structural alerts (SAs). This resulted in six (6) potential methods for elucidating TTCs: In vivo rodent micronucleus assay/ LD50, Benigni-Bossa/ LD50, Cramer extended/ LD50, In vivo rodent micronucleus assay/ TDLo, Benigni-Bossa/ TDLo, and the Cramer extended/ TDLo. After each algorithm designated two structural families each, the distribution of TDLo's and LD50's for each structural family was subjected to a preliminary data analysis using JMP statistical software version 9. Based on an analysis of quantiles, skew, and kurtosis, it was concluded that the TDLo dataset was of poor quality and was dropped from further analysis, and that the In vivo rodent micronucleus assay algorithm failed to partition the initial test set in a meaningful way, so it too was culled from further consideration. This resulted in (2) remaining TTC methods for further consideration: Benigni-Bossa/ LD50 and the Cramer extended/ LD50. The remaining methods were subjected to internal validation based on Gene-Tox, CCRIS, CPDB, IARC, and EPA classaifications for genotoxic mutagenicity and carcinogenicity. Validation parameters were calculated for both methods and it was determined that the Benigni-Bossa/ LD50 method outperformed the Cramer extended/ LD50 method in terms of specificity (87.2 vs. 48.1%#37;), accuracy (65.2 vs. 52.94%#37;), positive predictivity (66.6 vs. 50%#37;), negative predictivity (64.8 vs. 56.5%#37;), ROC+ (2 vs. 1) and ROC- (1.84 vs. 1.3). These results indicated that the Benigni-Bossa/ LD50 was the most appropriate for calculating TTCs for vaccine constituents. For each class, the lower 2.5th percentile LD50 was extrapolated to a TTC value using safety estimates derived using uncertainty factors (UF) and adjusting for adult human weight. Final TTCs were designated as 18.06 μg/ person and 20.616 μg/ person for the Benigni-Bossa positive and negative structural families.

Pedestrian and cyclist collisions with motor vehicles are a growing problem in the United States and in particular Austin, Texas. These collisions cause unnecessary loss of life and injury. This research explores strategies in the realms of engineering, education and enforcement from three leading cities for pedestrian and cyclist safety. Based on the analysis, I have identified possible strategies for use in Austin, Texas to prevent these collision types. I also offer a conceptual model that can be used as a framework for organizing and thinking about the various components involved in preventing pedestrian and cyclist collisions with motor vehicles. / text

Faced with continuously increasing maintenance due to aging infrastructure, the Texas Department of Transportation (TxDOT) is evaluating the potential impact of reduced funding on highway safety. The main objective of this thesis is to develop a methodological procedure to identify threshold levels of pavement skid resistance for highways in the context of traffic crashes, assisting TxDOT Administration and engineers in making proper maintenance decisions. As a result, the efficiency and safety of the highway system could be preserved. The scope of this study covers all types of state-maintained highways in Texas. The primary objectives of this thesis include: 1) synthesis of literature; 2) quantification of the relationship between crash risk and pavement skid resistant; 3) determination of critical skid resistant threshold levels; and, 4) benefit cost analysis. A detailed methodology framework was developed and a comprehensive database was generated from four data files containing pavement, geometry, traffic, and crash information to support this research. The impact of skid resistance level on crash risks was proven to be significant based on the results of regression analysis and insights provided by TxDOT experts. The quantitative relationships between crash risk and skid resistance were quantified using the Crash Rate Ratio method. Hierarchical structure grouping was used to categorize the entire network into homogeneous groups based on traffic level, roadway alignment and other factors. Critical skid resistance threshold levels were determined for the whole state as well as for stratified highway groups. Finally, benefit/cost ratio analyses were conducted to evaluate the effectiveness of pavement maintenance treatments to restore or increase skid resistance. / text

Keeping stakeholders far from danger is even more urgent for the construction industry which features higher than average accident and fatality rates worldwide. Improving safety proactively and thus saving huge losses incurred through cultivating safety climate (i.e. people’s perception and attitude of safety policies, procedures, and practices at workplaces) has been advocated and studied since 1980s. Nevertheless, the issue remains that what are the antecedents and how do they impact on safety climate and hence safety behavior at the individual level. With the construction industry of Hong Kong in perspective, a plateau of accident statistics reached since the entry into the new millennium calls for research into possible human factors behind the scene. Against such backdrop, the investigation is carried out in an attempt to tackle the issue with both theoretical and practical implications. With the aim at a better understanding of the research question, a two-stage mixed method research design featured with both qualitative and quantitative approaches is adopted. At the first stage, based on extant literature and 17 interviews with local construction practitioners, antecedents of safety climate are ascertained and categorized into five general perspectives, i.e. structural perspective, perceptual perspective, interactive perspective, cultural perspective, and to-be-confirmed perspective capturing factors not belonging to the first four perspectives. To increase the conceptual precision of safety climate and reveal the working mechanism of safety climate, a series of safety climate related outcomes are integrated into an initially hypothesized research model. Measurement instruments and practical relevance of latent constructs of interest are obtained by literature review and interviews. At the second stage, a large scale questionnaire survey targeting at construction practitioners across Hong Kong and case study of a local civil engineering project are conducted concurrently. Based on 292 valid responses, most of the bi-variate correlations between constructs demonstrate support for the hypothesized relationships, despite of some unexpectedly weak effects implied by path coefficients of the initial structural model. After modification based on theory and practice, the modified structural model reveals four routes to forming safety climate, i.e. 1) sound organizational climate through fluent leader-member exchange; 2) client involvement via enforcing safety management system; 3) individualism leading to negative safety climate; and 4) sound supervisory practice contributing to positive safety climate. Furthermore, the revised model confirms the previously found relationships among safety climate and its related outcomes. Learning from the case study which involves six interviews, participant observations of onsite meetings, and analysis of documents including safety plan, safety manual, minutes of safety related meetings, and content analysis of the primary 17 interviews generally corroborate the findings. Taken together, the research achieves the established objectives, provides a framework for future investigations into antecedents of safety climate, and hence suggests that safety is an emergent property of a complicated socio-technical system, involving diversifying factors. The implications of the findings have for devising safety interventions are discussed in the conclusion section, along with limitations and future research directions. / published_or_final_version / Real Estate and Construction / Doctoral / Doctor of Philosophy

Background: Long outpatient waiting time is a significant problem in Mainland China’s healthcare system. Long patient waiting time negatively affects actual care quality as well as patients’ perceptions of medical care. Aim: This study aims to understand the causes of long patient wait times in China’s outpatient care departments, and how those waits influence patients’ attitudes towards medical care. The rhythm of hospital patient flow will be explored in order to posit modest suggestions to resolve these issues. Objectives: The objectives of this study are to identify the causes of long waiting times in China’s outpatient care departments, to distinguish the specific bottleneck points in patient flow, and to characterize the relationship between waiting time length and the patients’ perceptions of medical care. Method: Two tertiary care hospitals in Mainland China were included as study sites. Macroergonomic methodologies were adopted to guide the data collection and analysis. The Systems Engineering Initiative for Patient Safety (SEIPS) model was specifically adopted to guide the study design and data analysis procedures. First, audio records were made of interviews with care providers from the two hospitals in order to document and discern the causes of long outpatient care waiting times. Second, a time study was carried out with patients visiting two outpatient departments at the two study sites in order to identify inefficiencies and bottleneck points in the patient flow. Third, a questionnaire survey was provided to the patients in order to understand the impact of lengthy wait times on their overall perceptions of medical care. The interview data was analyzed using content analysis methods, time study data was used to generate a patient flow model, and the questionnaire feedback was analyzed in tandem with the time study data using a linear regression analysis. Results: Sixty-three factors contributing to lengthy patient wait time were discerned from the interview data, concerning each of the five dimensions of the SEIPS model work system. Two patient flow diagrams were designed based on identified patient flow inefficiencies and bottlenecks. A majority (four-fifths and three-quarters, respectively, at the two study sites) of total patient visit time was spent on waiting for physician services and ancillary, non-medical activities. Serious bottlenecks in patient flow occurred while waiting for physician consultation, ultrasound examinations, and medical test result feedback. Patients’ evaluations of medical care quality dropped 0.04 points for each minute of consultation wait time, and 0.02 points for each minute of total visit duration and total waiting time. Conclusions: The causes of long patient wait times concern the physicians’ and patients’ characteristics, the organization and management of the hospital, the tasks, technology, and tools involved, and the hospital environment. Waiting for physician consultation, ultrasound examinations, and medical test result feedback cause the most patient flow problems. Long wait times have an adverse impact upon patients’ perceptions of medical care. The macroergonomic methodologies prove feasible and effective in evaluating health care systems. / published_or_final_version / Industrial and Manufacturing Systems Engineering / Master / Master of Philosophy

In view of the 911 terrorist incident plus various cases regarding undeclared dangerous goods were happened, tightening security measure on air cargo was adopted by different governments. Additional requirement of cargo screening would involve extra cost and thus the competitiveness of Hong Kong in the industry may weaken. Concern about that the compliance of new security requirement would affect Hong Kong economy and adversely affect the position of Hong Kong International Airport as an international air cargo hub. There are implications of the trend of having tightening of security measures on air cargo in Hong Kong. This study will examine the development of international air cargo security requirement, focusing on the potential solutions and cost implications for Hong Kong air cargo industry. It is expected that the research results will outline the practical solutions and provide a platform for further academic research analysis on providing recommendations to facilitate the aviation security requirement development in Hong Kong. / published_or_final_version / Transport Policy and Planning / Master / Master of Arts in Transport Policy and Planning

Managing safety in the energy industry requires continuous assessment of the factors with potential to contribute to accidents. Investigations into major incidents across highhazard industries have repeatedly highlighted the critical role of management factors in relation to safety performance. As leadership from site-level managers has been identified as a key non-technical skill with potential to measurably affect safety variables, this thesis investigates how the concept of ‘safety leadership,’ a term commonly used in the energy industry, might be applied at the level of senior management. After a review of the empirical literature revealed minimal consistency across existing work on this topic, four studies were conducted to support the operationalisation of the term ‘safety leadership’ in language relevant to practicing managers. In the first study (Study 1) semistructured interviews with subject matter experts (19 senior managers, 3 health and safety professionals) supported the identification of a set of behavioural ‘elements’ of safety leadership. In Study 2, a second set of interviews with contractors (n=11) and regulators (n=11) facilitated the refinement of the element set, and a preliminary safety leadership framework was proposed wherein behavioural elements were organised into broader categories. In Study 3, a documentary analysis study, data from published incident reports from the energy industry were used to test the preliminary safety leadership framework and assess the framework’s capacity to encompass senior-level behaviours that have been implicated in major investigations. Finally, Study 4 used structured interviews with experienced senior managers (n=15) to assess the face and content validity of the framework. This research informed the development of a behavioural framework, labelled the safety leadership framework (SLF), that includes three categories (Maintaining risk awareness, Leads by example, Setting and managing safety standards) encompassing seven safety leadership elements (Promotes continuous exchange of safety information, Monitors the reality of operations, Incorporates safety into decision-making, Acts as a safety role model, Provides direction, Reinforces with rewards and consequences, Supports and motivates)

<p> Personnel who work on the flight deck of an aircraft carrier are exposed to extreme levels of jet engine noise often in excess of 140 decibels (dB). The current circumaural hearing protective devices (CAHPD) employed by flight deck crewmen are inadequate for the level of protection required for these extreme levels of noise. Fiber-reinforced thermoset polymer composite (FRPC) materials such as aramid fibers used in body armor, have high theoretical values of acoustic impedance due to a fundamentally high modulus of elasticity and may offer a superior level of hearing protection over original equipment (OE) thermoplastic CAHPDs. The objective of this project was to measure and evaluate the attenuation of CAHPD&rsquo;s constructed from FRPC materials. FRPC CAHPD ear cups were paired with OE thermoplastic CAHPD ear cups of equal shape and thickness, and the protected and unprotected A-weighted sound pressure level (SPL) was measured in continuous and impulse noise environments >80 dBA using a JOLENE manikin. These data were evaluated for paired differences between the protected and unprotected mean SPL, and OE protected and FRPC protected mean SPL and indicates that OE thermoplastic CAHPDs provide greater sound attenuation of continuous noise >80 dBA and aramid FRPC CAHPDs provide greater sound attenuation of impulse noise >80 dBA.</p>

In the last decade modern information technology systems have been introduced to healthcare in order to improve it. The aim of this study is to present the impact of such information system’s adoption on patient safety and efficiency within healthcare. Interviews, observations along with literature study were conducted in order to study the impact of the adoption on patient safety and efficiency at hospital’s wards where a new information system is implemented. The conclusion of this study is that such information technology systems can improve patient safety. However it is believed that the information technology system can improve efficiency in some aspects such as the communication among medical care personnel while other aspects within efficiency can be achieved if some improvements are made. Moreover the ability to access Electronic Healthcare Records is considered to be important to improve the medical care, which can increase patient safety.

In this work we focus on building local maps to enable wheeled mobile robots to navigate safely and autonomously in urban environments. Urban environments present a variety of hazards that mobile robots have to detect and represent in their maps to navigate safely. Examples of hazards include obstacles such as furniture, drop-offs such as at downward stairs, and inclined surfaces such as wheelchair ramps. We address two shortcomings perceived in the literature on mapping. The first is the extensive use of expensive laser-based sensors for mapping, and the second is the focus on only detecting obstacles when clearly other hazards such as drop-offs need to be detected to ensure safety. Therefore, in this work we develop algorithms for building maps using only relatively inexpensive stereo cameras, that allow safe local navigation by detecting and modeling hazards such as overhangs, drop-offs, and ramps in addition to static obstacles. The hazards are represented using 2D annotated grid maps called local safety maps. Each cell in the map is annotated with one of several labels: Level, Inclined, Non-ground, or, Unknown. Level cells are safe for travel whereas Inclined cells require caution. Non-ground cells are unsafe for travel and represent obstacles, overhangs, or regions lower than safe ground. Level and Inclined cells can be further annotated as being Drop-off Edges. The process of building safety maps consists of three main steps: (i) computing a stereo depth map; (ii) building a 3D model using the stereo depths; and, (iii) analyzing the 3D model for safety to construct the safety map. We make significant contributions to each of the three steps: we develop global stereo methods for computing disparity maps that use edge and color information; we introduce a probabilistic data association method for building 3D models using stereo range points; and we devise a novel method for segmenting and fitting planes to 3D models allowing for a precise safety analysis. In addition, we also develop a stand-alone method for detecting drop-offs in front of the robot that uses motion and occlusion cues and only relies on monocular images. We introduce an evaluation framework for evaluating (and comparing) our algorithms on real world data sets, collected by driving a robot in various environments. Accuracy is measured by comparing the constructed safety maps against ground truth safety maps and computing error rates. The ground truth maps are obtained by manually annotating maps built using laser data. As part of the framework we also estimate latencies introduced by our algorithms and the accuracy of the plane fitting process. We believe this framework can be used for comparing the performance of a variety of vision-based mapping systems and for this purpose we make our datasets, ground truth maps, and evaluation code publicly available. We also implement a real-time version of one of the safety map algorithms on a wheelchair robot and demonstrate it working in various environments. The constructed safety maps allow safe local motion planning and also support the extraction of local topological structures that can be used to build global maps. / text