647 resultados para Macrophage Migration-Inhibitory Factors


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Police work tasks are diverse and require the ability to take command, demonstrate leadership, make serious decisions and be self directed (Beck, 1999; Brunetto & Farr-Wharton, 2002; Howard, Donofrio & Boles, 2002). This work is usually performed in pairs or sometimes by an officer working alone. Operational police work is seldom performed under the watchful eyes of a supervisor and a great amount of reliance is placed on the high levels of motivation and professionalism of individual officers. Research has shown that highly motivated workers produce better outcomes (Whisenand & Rush, 1998; Herzberg, 2003). It is therefore important that Queensland police officers are highly motivated to provide a quality service to the Queensland community. This research aims to identify factors which motivate Queensland police to perform quality work. Researchers acknowledge that there is a lack of research and knowledge in regard to the factors which motivate police (Beck, 1999; Bragg, 1998; Howard, Donofrio & Boles, 2002; McHugh & Verner, 1998). The motivational factors were identified in regard to the demographic variables of; age, sex, rank, tenure and education. The model for this research is Herzberg’s two-factor theory of workplace motivation (1959). Herzberg found that there are two broad types of workplace motivational factors; those driven by a need to prevent loss or harm and those driven by a need to gain personal satisfaction or achievement. His study identified 16 basic sub-factors that operate in the workplace. The research utilised a questionnaire instrument based on the sub-factors identified by Herzberg (1959). The questionnaire format consists of an initial section which sought demographic information about the participant and is followed by 51 Likert scale questions. The instrument is an expanded version of an instrument previously used in doctoral studies to identify sources of police motivation (Holden, 1980; Chiou, 2004). The questionnaire was forwarded to approximately 960 police in the Brisbane, Metropolitan North Region. The data were analysed using Factor Analysis, MANOVAs, ANOVAs and multiple regression analysis to identify the key sources of police motivation and to determine the relationships between demographic variables such as: age, rank, educational level, tenure, generation cohort and motivational factors. A total of 484 officers responded to the questionnaire from the sample population of 960. Factor analysis revealed five broad Prime Motivational Factors that motivate police in their work. The Prime Motivational Factors are: Feeling Valued, Achievement, Workplace Relationships, the Work Itself and Pay and Conditions. The factor Feeling Valued highlighted the importance of positive supportive leaders in motivating officers. Many officers commented that supervisors who only provided negative feedback diminished their sense of feeling valued and were a key source of de-motivation. Officers also frequently commented that they were motivated by operational police work itself whilst demonstrating a strong sense of identity with their team and colleagues. The study showed a general need for acceptance by peers and an idealistic motivation to assist members of the community in need and protect victims of crime. Generational cohorts were not found to exert a significant influence on police motivation. The demographic variable with the single greatest influence on police motivation was tenure. Motivation levels were found to drop dramatically during the first two years of an officer’s service and generally not improve significantly until near retirement age. The findings of this research provide the foundation of a number of recommendations in regard to police retirement, training and work allocation that are aimed to improve police motivation levels. The five Prime Motivational Factor model developed in this study is recommended for use as a planning tool by police leaders to improve motivational and job-satisfaction components of police Service policies. The findings of this study also provide a better understanding of the current sources of police motivation. They are expected to have valuable application for Queensland police human resource management when considering policies and procedures in the areas of motivation, stress reduction and attracting suitable staff to specific areas of responsibility.

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Recently it has been shown that the consumption of a diet high in saturated fat is associated with impaired insulin sensitivity and increased incidence of type 2 diabetes. In contrast, diets that are high in monounsaturated fatty acids (MUFAs) or polyunsaturated fatty acids (PUFAs), especially very long chain n-3 fatty acids (FAs), are protective against disease. However, the molecular mechanisms by which saturated FAs induce the insulin resistance and hyperglycaemia associated with metabolic syndrome and type 2 diabetes are not clearly defined. It is possible that saturated FAs may act through alternative mechanisms compared to MUFA and PUFA to regulate of hepatic gene expression and metabolism. It is proposed that, like MUFA and PUFA, saturated FAs regulate the transcription of target genes. To test this hypothesis, hepatic gene expression analysis was undertaken in a human hepatoma cell line, Huh-7, after exposure to the saturated FA, palmitate. These experiments showed that palmitate is an effective regulator of gene expression for a wide variety of genes. A total of 162 genes were differentially expressed in response to palmitate. These changes not only affected the expression of genes related to nutrient transport and metabolism, they also extend to other cellular functions including, cytoskeletal architecture, cell growth, protein synthesis and oxidative stress response. In addition, this thesis has shown that palmitate exposure altered the expression patterns of several genes that have previously been identified in the literature as markers of risk of disease development, including CVD, hypertension, obesity and type 2 diabetes. The altered gene expression patterns associated with an increased risk of disease include apolipoprotein-B100 (apo-B100), apo-CIII, plasminogen activator inhibitor 1, insulin-like growth factor-I and insulin-like growth factor binding protein 3. This thesis reports the first observation that palmitate directly signals in cultured human hepatocytes to regulate expression of genes involved in energy metabolism as well as other important genes. Prolonged exposure to long-chain saturated FAs reduces glucose phosphorylation and glycogen synthesis in the liver. Decreased glucose metabolism leads to elevated rates of lipolysis, resulting in increased release of free FAs. Free FAs have a negative effect on insulin action on the liver, which in turn results in increased gluconeogenesis and systemic dyslipidaemia. It has been postulated that disruption of glucose transport and insulin secretion by prolonged excessive FA availability might be a non-genetic factor that has contributed to the staggering rise in prevalence of type 2 diabetes. As glucokinase (GK) is a key regulatory enzyme of hepatic glucose metabolism, changes in its activity may alter flux through the glycolytic and de novo lipogenic pathways and result in hyperglycaemia and ultimately insulin resistance. This thesis investigated the effects of saturated FA on the promoter activity of the glycolytic enzyme, GK, and various transcription factors that may influence the regulation of GK gene expression. These experiments have shown that the saturated FA, palmitate, is capable of decreasing GK promoter activity. In addition, quantitative real-time PCR has shown that palmitate incubation may also regulate GK gene expression through a known FA sensitive transcription factor, sterol regulatory element binding protein-1c (SREBP-1c), which upregulates GK transcription. To parallel the investigations into the mechanisms of FA molecular signalling, further studies of the effect of FAs on metabolic pathway flux were performed. Although certain FAs reduce SREBP-1c transcription in vitro, it is unclear whether this will result in decreased GK activity in vivo where positive effectors of SREBP-1c such as insulin are also present. Under these conditions, it is uncertain if the inhibitory effects of FAs would be overcome by insulin. The effects of a combination of FAs, insulin and glucose on glucose phosphorylation and metabolism in cultured primary rat hepatocytes at concentrations that mimic those in the portal circulation after a meal was examined. It was found that total GK activity was unaffected by an increased concentration of insulin, but palmitate and eicosapentaenoic acid significantly lowered total GK activity in the presence of insulin. Despite the fact that total GK enzyme activity was reduced in response to FA incubation, GK enzyme translocation from the inactive, nuclear bound, to active, cytoplasmic state was unaffected. Interestingly, none of the FAs tested inhibited glucose phosphorylation or the rate of glycolysis when insulin is present. These results suggest that in the presence of insulin the levels of the active, unbound cytoplasmic GK are sufficient to buffer a slight decrease in GK enzyme activity and decreased promoter activity caused by FA exposure. Although a high fat diet has been associated with impaired hepatic glucose metabolism, there is no evidence from this thesis that FAs themselves directly modulate flux through the glycolytic pathway in isolated primary hepatocytes when insulin is also present. Therefore, although FA affected expression of a wide range of genes, including GK, this did not affect glycolytic flux in the presence of insulin. However, it may be possible that a saturated FA-induced decrease in GK enzyme activity when combined with the onset of insulin resistance may promote the dys-regulation of glucose homeostasis and the subsequent development of hyperglycaemia, metabolic syndrome and type 2 diabetes.