Endothelin 3 induces skin pigmentation in a keratin-driven inducible mouse model

Endothelin 3 (Edn3) is a ligand important to developing neural crest cells (NCC). Some NCC eventually migrate into the skin and give rise to the pigment-forming melanocytes found in hair follicles. Edn3's effects on NCC have been largely explored through spontaneous mutants and cell culture experiments. These studies have shown the Endothelin receptor B/Edn3 signaling pathway to be important in the proliferation/survival and differentiation of developing melanocytes. To supplement these investigations I have created doxycycline-responsive transgenic mice which conditionally over-express Edn3. These mice will help us clarify Edn3's role during the development of early embryonic melanoblasts, differentiating melanocyte precursors in the skin, and fully differentiated melanocytes in the hair follicle. The transgene mediated expression of Edn3 was predominantly confined to the roof plate of the neural tube and surface ectoderm in embryos and postnatally in the epidermal keratinocytes of the skin. Relative to littermate controls, transgenics develop increased pigmentation on most areas of the skin. My doxycycline-based temporal studies have shown that both embryonic and postnatal events are important for establishing and maintaining pigmented skin. The study of my Edn3 transgenic mice may offer some insight into the genetics behind benign dermal pigmentation and offer clues about the time periods important in establishing these conditions. This apparently abnormal development is echoed in a benign condition of human skin. Cases of dermal melanocytosis, such as common freckles, Mongolian spotting, and nevus of Ito demonstrate histological and etiological characteristics similar to those of the transgenic mice generated in this study.

Food Safety in Restaurants: A Human Relations Model

Barry Reece and Rhonda Brandt use a human relations perspective to explain behavior at work. Following a review of the six components of their model, the author presents research to illustrate how it can be used by managers to help them understand why food safety violations occur in restaurants. An additional variable not included in the model is discusses and recommendations for managers are made.

Predicting employee compliance with safety regulations, factoring risk perception

The purpose of this research was to develop a methodology that would evaluate employees' personality traits, demographic characteristics, and workplace parameters to predict safety compliance along with the moderating effect of risk perception. ^ One hundred and twenty five employees of a manufacturing facility were given questionnaires to gather their demographic and perception information. Surveys were also used to measure their personality characteristics, and periodic observations were recorded to document employee's safety compliance. A significant correlation was found between compliance and the worker's perception of management's commitment to safety (r = 0.27, p < 0.01), as well as with gender (r = −0.19, p < 0.05). Females showed a significantly higher average compliance (78%), than males (69%). These findings demonstrated the value of developing a model to predict safety behavior that would assist companies in maintaining a safe work environment, preventing accidents, ensuring compliance, and reducing associated costs. ^

Development of safety performance functions for empirical Bayes estimation of crash reduction factors

Crash reduction factors (CRFs) are used to estimate the potential number of traffic crashes expected to be prevented from investment in safety improvement projects. The method used to develop CRFs in Florida has been based on the commonly used before-and-after approach. This approach suffers from a widely recognized problem known as regression-to-the-mean (RTM). The Empirical Bayes (EB) method has been introduced as a means to addressing the RTM problem. This method requires the information from both the treatment and reference sites in order to predict the expected number of crashes had the safety improvement projects at the treatment sites not been implemented. The information from the reference sites is estimated from a safety performance function (SPF), which is a mathematical relationship that links crashes to traffic exposure. The objective of this dissertation was to develop the SPFs for different functional classes of the Florida State Highway System. Crash data from years 2001 through 2003 along with traffic and geometric data were used in the SPF model development. SPFs for both rural and urban roadway categories were developed. The modeling data used were based on one-mile segments that contain homogeneous traffic and geometric conditions within each segment. Segments involving intersections were excluded. The scatter plots of data show that the relationships between crashes and traffic exposure are nonlinear, that crashes increase with traffic exposure in an increasing rate. Four regression models, namely, Poisson (PRM), Negative Binomial (NBRM), zero-inflated Poisson (ZIP), and zero-inflated Negative Binomial (ZINB), were fitted to the one-mile segment records for individual roadway categories. The best model was selected for each category based on a combination of the Likelihood Ratio test, the Vuong statistical test, and the Akaike's Information Criterion (AIC). The NBRM model was found to be appropriate for only one category and the ZINB model was found to be more appropriate for six other categories. The overall results show that the Negative Binomial distribution model generally provides a better fit for the data than the Poisson distribution model. In addition, the ZINB model was found to give the best fit when the count data exhibit excess zeros and over-dispersion for most of the roadway categories. While model validation shows that most data points fall within the 95% prediction intervals of the models developed, the Pearson goodness-of-fit measure does not show statistical significance. This is expected as traffic volume is only one of the many factors contributing to the overall crash experience, and that the SPFs are to be applied in conjunction with Accident Modification Factors (AMFs) to further account for the safety impacts of major geometric features before arriving at the final crash prediction. However, with improved traffic and crash data quality, the crash prediction power of SPF models may be further improved.

Achieving zero accidents—A strategic framework for continuous safety improvement in the construction industry

In the U.S., construction accidents remain a significant economic and social problem. Despite recent improvement, the Construction industry, generally, has lagged behind other industries in implementing safety as a total management process for achieving zero accidents and developing a high-performance safety culture. One aspect of this total approach to safety that has frustrated the construction industry the most has been “measurement”, which involves identifying and quantifying the factors that critically influence safe work behaviors. The basic problem attributed is the difficulty in assessing what to measure and how to measure it—particularly the intangible aspects of safety. Without measurement, the notion of continuous improvement is hard to follow. This research was undertaken to develop a strategic framework for the measurement and continuous improvement of total safety in order to achieve and sustain the goal of zero accidents, while improving the quality, productivity and the competitiveness of the construction industry as it moves forward. The research based itself on an integral model of total safety that allowed decomposition of safety into interior and exterior characteristics using a multiattribute analysis technique. Statistical relationships between total safety dimensions and safety performance (measured by safe work behavior) were revealed through a series of latent variables (factors) that describe the total safety environment of a construction organization. A structural equation model (SEM) was estimated for the latent variables to quantify relationships among them and between these total safety determinants and safety performance of a construction organization. The developed SEM constituted a strategic framework for identifying, measuring, and continuously improving safety as a total concern for achieving and sustaining the goal of zero accidents.

Development of safety performance functions for SafetyAnalyst applications in Florida

In 2010, the American Association of State Highway and Transportation Officials (AASHTO) released a safety analysis software system known as SafetyAnalyst. SafetyAnalyst implements the empirical Bayes (EB) method, which requires the use of Safety Performance Functions (SPFs). The system is equipped with a set of national default SPFs, and the software calibrates the default SPFs to represent the agency's safety performance. However, it is recommended that agencies generate agency-specific SPFs whenever possible. Many investigators support the view that the agency-specific SPFs represent the agency data better than the national default SPFs calibrated to agency data. Furthermore, it is believed that the crash trends in Florida are different from the states whose data were used to develop the national default SPFs. In this dissertation, Florida-specific SPFs were developed using the 2008 Roadway Characteristics Inventory (RCI) data and crash and traffic data from 2007-2010 for both total and fatal and injury (FI) crashes. The data were randomly divided into two sets, one for calibration (70% of the data) and another for validation (30% of the data). The negative binomial (NB) model was used to develop the Florida-specific SPFs for each of the subtypes of roadway segments, intersections and ramps, using the calibration data. Statistical goodness-of-fit tests were performed on the calibrated models, which were then validated using the validation data set. The results were compared in order to assess the transferability of the Florida-specific SPF models. The default SafetyAnalyst SPFs were calibrated to Florida data by adjusting the national default SPFs with local calibration factors. The performance of the Florida-specific SPFs and SafetyAnalyst default SPFs calibrated to Florida data were then compared using a number of methods, including visual plots and statistical goodness-of-fit tests. The plots of SPFs against the observed crash data were used to compare the prediction performance of the two models. Three goodness-of-fit tests, represented by the mean absolute deviance (MAD), the mean square prediction error (MSPE), and Freeman-Tukey R2 (R2FT), were also used for comparison in order to identify the better-fitting model. The results showed that Florida-specific SPFs yielded better prediction performance than the national default SPFs calibrated to Florida data. The performance of Florida-specific SPFs was further compared with that of the full SPFs, which include both traffic and geometric variables, in two major applications of SPFs, i.e., crash prediction and identification of high crash locations. The results showed that both SPF models yielded very similar performance in both applications. These empirical results support the use of the flow-only SPF models adopted in SafetyAnalyst, which require much less effort to develop compared to full SPFs.

A computer simulation model for single -lane roundabouts

During the past three decades, the use of roundabouts has increased throughout the world due to their greater benefits in comparison with intersections controlled by traditional means. Roundabouts are often chosen because they are widely associated with low accident rates, lower construction and operating costs, and reasonable capacities and delay. ^ In the planning and design of roundabouts, special attention should be given to the movement of pedestrians and bicycles. As a result, there are several guidelines for the design of pedestrian and bicycle treatments at roundabouts that increase the safety of both pedestrians and bicyclists at existing and proposed roundabout locations. Different design guidelines have differing criteria for handling pedestrians and bicyclists at roundabout locations. Although all of the investigated guidelines provide better safety (depending on the traffic conditions at a specific location), their effects on the performance of the roundabout have not been examined yet. ^ Existing roundabout analysis software packages provide estimates of capacity and performance characteristics. This includes characteristics such as delay, queue lengths, stop rates, effects of heavy vehicles, crash frequencies, and geometric delays, as well as fuel consumption, pollutant emissions and operating costs for roundabouts. None of these software packages, however, are capable of determining the effects of various pedestrian crossing locations, nor the effect of different bicycle treatments on the performance of roundabouts. ^ The objective of this research is to develop simulation models capable of determining the effect of various pedestrian and bicycle treatments at single-lane roundabouts. To achieve this, four models were developed. The first model simulates a single-lane roundabout without bicycle and pedestrian traffic. The second model simulates a single-lane roundabout with a pedestrian crossing and mixed flow bicyclists. The third model simulates a single-lane roundabout with a combined pedestrian and bicycle crossing, while the fourth model simulates a single-lane roundabout with a pedestrian crossing and a bicycle lane at the outer perimeter of the roundabout for the bicycles. Traffic data was collected at a modern roundabout in Boca Raton, Florida. ^ The results of this effort show that installing a pedestrian crossing on the roundabout approach will have a negative impact on the entry flow, while the downstream approach will benefit from the newly created gaps by pedestrians. Also, it was concluded that a bicycle lane configuration is more beneficial for all users of the roundabout instead of the mixed flow or combined crossing. Installing the pedestrian crossing at one-car length is more beneficial for pedestrians than two- and three-car lengths. Finally, it was concluded that the effect of the pedestrian crossing on the vehicle queues diminishes as the distance between the crossing and the roundabout increases. ^

An examination of psychological meaningfulness, safety, and availability as the underlying mechanisms linking job features and personal characteristics to work engagement

The present study tested a nomological net of work engagement that was derived from its extant research. Two of the main work engagement models that have been presented and empirically tested in the literature, the JD-R model and Kahn's model, were integrated to test the effects that job features and personal characteristics can have on work engagement through the psychological conditions of meaningfulness, safety, and availability. In this study, safety refers to psychological perceptions of safety and not workplace safety behaviors. The job features that were tested in this model included person-job fit, autonomy, co-worker relations, supervisor support, procedural justice, and interactional justice, while the personal characteristics consisted of self-consciousness, self-efficacy, extraversion, and neuroticism. Thirty-four hypotheses and a conceptual model were tested in order to establish the viability of this nomological net of work engagement in which it was expected that meaningfulness would mediate the relationships between job features and work engagement, safety would mediate the relationships that job features and personal characteristics have with work engagement, and availability (physical, emotional, and cognitive resources) would mediate the relationships that personal characteristics have with work engagement. Furthermore, analyses were run in order to determine the factor structure of work engagement, assess whether or not it exhibits differential validity from organizational commitment and job satisfaction, and confirm that it is positively related to the outcome variable of organizational citizenship behavior (OCB). The final sample consisted of 500 workers from an online labor market who responded to a questionnaire composed of measures of all constructs included in this study. Findings show that work engagement is best represented as a three-factor construct, composed of vigor, dedication and absorption. Furthermore, support was found for the distinction of work engagement from the related constructs of organizational commitment and job satisfaction. With regard to the proposed model, meaningfulness proved to be the strongest predictor of work engagement. Results show that it partially mediates the relationships that all job features have with work engagement. Safety proved to be a partial mediator of the relationships that autonomy, co-worker relations, supervisor support, procedural justice, interactional justice, and self-efficacy have with work engagement, and fully mediate the relationship between neuroticism and work engagement. Findings also show that availability partially mediates the positive relationships that extraversion and self-efficacy have with work engagement, and fully mediates the negative relationship that neuroticism has with work engagement. Finally, a positive relationship was found between work engagement and OCB. Research and organizational implications are discussed.

Effects of Endothelin 3 on the Tumor-Angiogenic Response in a Novel Melanoma Mouse Model

Skin cancer is the most common form of cancer in the United States. Melanoma is a particular type of skin cancer, which arises from the malignant transformation of melanocytes and generally exhibits a high propensity to metastasize. Melanoma progression is dependent on angiogenesis to deliver the oxygen and nutrients required to maintain the altered metabolism of rapidly proliferating tumorigenic cells. Recent studies have implicated the growth factor Endothelin 3 (Edn3) in melanoma progression and metastasis. The aim of this study was to examine the role that Edn3 plays in the angiogenesis of melanocytic lesions. For this purpose, Dct-Grm1 transgenic mice, which spontaneously acquire melanocytic lesions through the aberrant expression of the metabotropic glutamate receptor 1 (mGluR1), were crossed with K5-Edn3 transgenic mice that overexpress Edn3. Tumors in the Dct-Grm1/K5-Edn3 experimental population were examined and compared to the control Dct-Grm1 population using immuno-fluorescent staining targeted against the vascular endothelial cell marker CD31. Proteomic arrays were also used and identified changes in the expression of specific angiogenic factors. CD31 antibody staining results revealed an increased vascular density in Dct-Grm1/K5-Edn3 tumors compared with tumors from the Dct-Grm1 controls. Analysis of the relative expression of angiogenic proteins showed an upregulation of various vascular factors in tumors from the Dct-Grm1/K5-Edn3 population, including VEGF-B, MMP-8, MMP-9, and Angiogenin. These results suggest that endothelin signaling promotes angiogenesis in melanocytic lesions. Targeting the factors upregulated by Edn3 signaling may prove effective in hindering melanoma progression.

Personnel selection, safety performance, and job performance: Are safe workers better workers?

The present dissertation consists of two studies that combine personnel selection, safety performance, and job performance literatures to answer an important question: are safe workers better workers? Study 1 tested a predictive model of safety performance to examine personality characteristics (conscientiousness and agreeableness), and two novel behavioral constructs (safety orientation and safety judgment) as predictors of safety performance in a sample of forklift loaders/operators (N = 307). Analyses centered on investigating safety orientation as a proximal predictor and determinant of safety performance. Study 2 replicated Study 1 and explored the relationship between safety performance and job performance by testing an integrative model in a sample of machine operators and construction crewmembers (N = 323). Both Study 1 and Study 2 found conscientiousness, agreeableness, and safety orientation to be good predictors of safety performance. While both personality and safety orientation were positively related to safety performance, safety orientation proved to be a more proximal determinant of safety performance. Across studies, results surrounding safety judgment as a predictor of safety performance were inconclusive, suggesting possible issues with measurement of the construct. Study 2 found a strong relationship between safety performance and job performance. In addition, safety performance served as a mediator between predictors (conscientiousness, agreeableness and safety orientation) and job performance. Together these findings suggest that safe workers are indeed better workers, challenging previous viewpoints to the contrary. Further, results implicate the viability of personnel selection as means of promoting safety in organizations.^

UV-induced melanoma mouse model dependent on endothelin 3 over-expression

Melanoma is one of the most aggressive types of cancer. It originates from the transformation of melanocytes present in the epidermal/dermal junction of the human skin. It is commonly accepted that melanomagenesis is influenced by the interaction of environmental factors, genetic factors, as well as tumor-host interactions. DNA photoproducts induced by UV radiation are, in normal cells, repaired by the nucleotide excision repair (NER) pathway. The prominent role of NER in cancer resistance is well exemplified by patients with Xeroderma Pigmentosum (XP). This disease results from mutations in the components of the NER pathway, such as XPA and XPC proteins. In humans, NER pathway disruption leads to the development of skin cancers, including melanoma. Similar to humans afflicted with XP, Xpa and Xpc deficient mice show high sensibility to UV light, leading to skin cancer development, except melanoma. The Endothelin 3 (Edn3) signaling pathway is essential for proliferation, survival and migration of melanocyte precursor cells. Excessive production of Edn3 leads to the accumulation of large numbers of melanocytes in the mouse skin, where they are not normally found. In humans, Edn3 signaling pathway has also been implicated in melanoma progression and its metastatic potential. The goal of this study was the development of the first UV-induced melanoma mouse model dependent on the over-expression of Edn3 in the skin. The UV-induced melanoma mouse model reported here is distinguishable from all previous published models by two features: melanocytes are not transformed a priori and melanomagenesis arises only upon neonatal UV exposure. In this model, melanomagenesis depends on the presence of Edn3 in the skin. Disruption of the NER pathway due to the lack of Xpa or Xpc proteins was not essential for melanomagenesis; however, it enhanced melanoma penetrance and decreased melanoma latency after one single neonatal erythemal UV dose. Exposure to a second dose of UV at six weeks of age did not change time of appearance or penetrance of melanomas in this mouse model. Thus, a combination of neonatal UV exposure with excessive Edn3 in the tumor microenvironment is sufficient for melanomagenesis in mice; furthermore, NER deficiency exacerbates this process.^

UV-Induced Melanoma Mouse Model Dependent on Endothelin 3 Over-Expression

Melanoma is one of the most aggressive types of cancer. It originates from the transformation of melanocytes present in the epidermal/dermal junction of the human skin. It is commonly accepted that melanomagenesis is influenced by the interaction of environmental factors, genetic factors, as well as tumor-host interactions. DNA photoproducts induced by UV radiation are, in normal cells, repaired by the nucleotide excision repair (NER) pathway. The prominent role of NER in cancer resistance is well exemplified by patients with Xeroderma Pigmentosum (XP). This disease results from mutations in the components of the NER pathway, such as XPA and XPC proteins. In humans, NER pathway disruption leads to the development of skin cancers, including melanoma. Similar to humans afflicted with XP, Xpa and Xpc deficient mice show high sensibility to UV light, leading to skin cancer development, except melanoma. The Endothelin 3 (Edn3) signaling pathway is essential for proliferation, survival and migration of melanocyte precursor cells. Excessive production of Edn3 leads to the accumulation of large numbers of melanocytes in the mouse skin, where they are not normally found. In humans, Edn3 signaling pathway has also been implicated in melanoma progression and its metastatic potential. The goal of this study was the development of the first UV-induced melanoma mouse model dependent on the over-expression of Edn3 in the skin. The UV-induced melanoma mouse model reported here is distinguishable from all previous published models by two features: melanocytes are not transformed a priori and melanomagenesis arises only upon neonatal UV exposure. In this model, melanomagenesis depends on the presence of Edn3 in the skin. Disruption of the NER pathway due to the lack of Xpa or Xpc proteins was not essential for melanomagenesis; however, it enhanced melanoma penetrance and decreased melanoma latency after one single neonatal erythemal UV dose. Exposure to a second dose of UV at six weeks of age did not change time of appearance or penetrance of melanomas in this mouse model. Thus, a combination of neonatal UV exposure with excessive Edn3 in the tumor microenvironment is sufficient for melanomagenesis in mice; furthermore, NER deficiency exacerbates this process.

Development of Safety Performance Functions for SafetyAnalyst Applications in Florida

In 2010, the American Association of State Highway and Transportation Officials (AASHTO) released a safety analysis software system known as SafetyAnalyst. SafetyAnalyst implements the empirical Bayes (EB) method, which requires the use of Safety Performance Functions (SPFs). The system is equipped with a set of national default SPFs, and the software calibrates the default SPFs to represent the agency’s safety performance. However, it is recommended that agencies generate agency-specific SPFs whenever possible. Many investigators support the view that the agency-specific SPFs represent the agency data better than the national default SPFs calibrated to agency data. Furthermore, it is believed that the crash trends in Florida are different from the states whose data were used to develop the national default SPFs. In this dissertation, Florida-specific SPFs were developed using the 2008 Roadway Characteristics Inventory (RCI) data and crash and traffic data from 2007-2010 for both total and fatal and injury (FI) crashes. The data were randomly divided into two sets, one for calibration (70% of the data) and another for validation (30% of the data). The negative binomial (NB) model was used to develop the Florida-specific SPFs for each of the subtypes of roadway segments, intersections and ramps, using the calibration data. Statistical goodness-of-fit tests were performed on the calibrated models, which were then validated using the validation data set. The results were compared in order to assess the transferability of the Florida-specific SPF models. The default SafetyAnalyst SPFs were calibrated to Florida data by adjusting the national default SPFs with local calibration factors. The performance of the Florida-specific SPFs and SafetyAnalyst default SPFs calibrated to Florida data were then compared using a number of methods, including visual plots and statistical goodness-of-fit tests. The plots of SPFs against the observed crash data were used to compare the prediction performance of the two models. Three goodness-of-fit tests, represented by the mean absolute deviance (MAD), the mean square prediction error (MSPE), and Freeman-Tukey R2 (R2FT), were also used for comparison in order to identify the better-fitting model. The results showed that Florida-specific SPFs yielded better prediction performance than the national default SPFs calibrated to Florida data. The performance of Florida-specific SPFs was further compared with that of the full SPFs, which include both traffic and geometric variables, in two major applications of SPFs, i.e., crash prediction and identification of high crash locations. The results showed that both SPF models yielded very similar performance in both applications. These empirical results support the use of the flow-only SPF models adopted in SafetyAnalyst, which require much less effort to develop compared to full SPFs.

An Examination of Psychological Meaningfulness, Safety, and Availability as the Underlying Mechanisms linking Job Features and Personal Characteristics to Work Engagement

The present study tested a nomological net of work engagement that was derived from its extant research. Two of the main work engagement models that have been presented and empirically tested in the literature, the JD-R model and Kahn’s model, were integrated to test the effects that job features and personal characteristics can have on work engagement through the psychological conditions of meaningfulness, safety, and availability. In this study, safety refers to psychological perceptions of safety and not workplace safety behaviors. The job features that were tested in this model included person-job fit, autonomy, co-worker relations, supervisor support, procedural justice, and interactional justice, while the personal characteristics consisted of self-consciousness, self-efficacy, extraversion, and neuroticism. Thirty-four hypotheses and a conceptual model were tested in order to establish the viability of this nomological net of work engagement in which it was expected that meaningfulness would mediate the relationships between job features and work engagement, safety would mediate the relationships that job features and personal characteristics have with work engagement, and availability (physical, emotional, and cognitive resources) would mediate the relationships that personal characteristics have with work engagement. Furthermore, analyses were run in order to determine the factor structure of work engagement, assess whether or not it exhibits differential validity from organizational commitment and job satisfaction, and confirm that it is positively related to the outcome variable of organizational citizenship behavior (OCB). The final sample consisted of 500 workers from an online labor market who responded to a questionnaire composed of measures of all constructs included in this study. Findings show that work engagement is best represented as a three-factor construct, composed of vigor, dedication and absorption. Furthermore, support was found for the distinction of work engagement from the related constructs of organizational commitment and job satisfaction. With regard to the proposed model, meaningfulness proved to be the strongest predictor of work engagement. Results show that it partially mediates the relationships that all job features have with work engagement. Safety proved to be a partial mediator of the relationships that autonomy, co-worker relations, supervisor support, procedural justice, interactional justice, and self-efficacy have with work engagement, and fully mediate the relationship between neuroticism and work engagement. Findings also show that availability partially mediates the positive relationships that extraversion and self-efficacy have with work engagement, and fully mediates the negative relationship that neuroticism has with work engagement. Finally, a positive relationship was found between work engagement and OCB. Research and organizational implications are discussed.