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Correlation of MicroRNA Expressions with mutated and unmutated IgVH gene groups in chronic lymphocytic leukemiaZou, Yi 28 April 2005
B-cell chronic lymphocytic leukemia is the most common leukemia in the adult population of Western developed countries. In 2005, an estimated 9,730 adults in the United States will be diagnosed with B-CLL and an estimated 4,600 deaths will occur. B-CLL is a common heterogeneous malignant disease with variable outcome. B-CLL is divided into two groups based on whether somatic hypermutation is observed in the variable region of the immunoglobulin heavy-chain locus (IgVH). The two distinct groups are named mutated and unmutated. The B-CLL mutated group has a more favorable prognosis than the unmutated group.
Gene expression profiling has been used successfully to decipher the biological and clinical diversity of many leukemias and lymphomas. Recently, other small RNAs (microRNAs) have been shown to be important in hematopoiesis. MicroRNAs are small 20-28 nucleotide RNAs that are believed to control many important cellular and developmental processes by posttranscriptional gene silencing, translational repression, and modulating epigenetic events.
We are interested in whether microRNA expression correlates with the mutational status of IgVH. This study is significant in the following ways: (1) microRNAs may become surrogate markers for the mutational status of IgVH of B-CLL, which implies a more rapid diagnostic means as compared to the current practice, and (2) microRNAs, in the particular context of B-CLL, may play some significant roles in a gene regulatory network that is further responsible for chromosomal abnormalities found in B-CLL.
This thesis presents a study comparing microRNA expression in mutated and unmutated B-CLL groups. Instead of using a genome-wide expression profiling strategy, we selected a specific set of microRNAs based on their chromosome locations and mRNA targets. Specifically, we chose the following eight microRNAs (with their chromosomal abnormalities): mir16-1 (deletion 13), let-7i (trisomy 12), mir196-2 (trisomy 12), mir26a-2 (trisomy 12), mir-34b (deletion 11), mir-125b (deletion 11), mir-181C (trisomy 19), mir-125a (trisomy 19). We used solution hybridization assays to monitor the expression of microRNAs. We successfully characterized the microRNA expression in twelve B-CLL patient samples (eight mutated and four unmutated). Among the eight microRNAs examined, three (mir196-2, mir-125a, mir-125b) are not expressed in the two B-CLL groups, four (mir16-1, mir26a-2, let-7i, mir-34b) have significant differences in expressions over the two groups, and one (mir-181c) has no significant difference in expressions over the two groups.
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Impact of Aging on Morphine Analgesia and Associated Changes in μ-Opioid Receptor Binding and Expression in the Ventrolateral Periaqueductal GrayHanberry, Richard l, IV 10 November 2010 (has links)
Chronic pain in the aged is a widespread phenomenon, and morphine is the most commonly used narcotic analgesic for treatment. Despite that fact, there are relatively few published studies examining the impact of advanced age on morphine analgesia. We hypothesized that aged rats would be less sensitive to morphine than adults, and that aged animals would have reduced mu-opioid receptor (MOR) binding and expression in the ventrolateral periaqueductal gray, a brain region responsible for morphine analgesia. Using a model of persistent inflammatory pain, we found that morphine was significantly less effective in aged males compared to adult males, and that aged males and females experience a reduction in MOR binding and expression compared to adults. These results suggest that there are clear age differences in morphine efficacy, and that reductions in MOR binding and expression in the periaqueductal gray could underlie those differences.
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Personal creative activity, male chronic illness and perceived stress : an exploratory studyLabuik, Tara Jean 15 September 2010
The purpose of this exploratory study was to investigate whether personal creative activity predicted perceived stress in men living with a chronic physical illness. Personal creative activity was measured with the Creative Achievement Questionnaire (Carson, Peterson, & Higgins, 2005), select questions from the Flow Questionnaire (Collins, 2006), the Everyday Creativity Questionnaire (Ivcevic & Mayer, 2009) and the Creative Behaviour Inventory (Hocevar, 1979). Perceived stress was measured with the Perceived Stress Scale (Cohen, Kamarck, & Mermelstein, 1983). Sequential Multiple Regression was used to assess the relationship between personal creative activity and perceived stress levels of males with chronic illness. It was hypothesized that there would be a negative relationship between men‟s personal creative activity involvement and their perceived level of stress; that is, higher personal creative activity scores would be associated with lower perceived stress levels. This relationship was expected to be demonstrated by all men regardless of their diagnosis.<p>
Participants included 139 males with chronic illness (mean age: 50 years). Findings indicated that personal creative activity was not related to perceived stress. However the participants reported being involved in many different personal creative activities not included in the four creative measures, which may help explain the low scores on the creativity measures that may have skewed the data and resulted in low correlations. Age and number of symptoms were related to perceived stress. As the participants aged, their perceived stress decreased; and the more symptoms they reported, the higher their perceived stress. The strengths and limitations of the current study are outlined, along with implications for future research and practice. Future research is needed to further examine the relationship between creativity and perceived stress in men with chronic illness as well as to develop creativity measures that include more male-oriented activities.
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Wildlife surveillance systems : chronic wasting diseaseTataryn, Joanne Rosemary 17 September 2009
Increased demand for animal disease surveillance information has led to the development and refinement of methodologies for qualitative and quantitative surveillance system evaluations to maximize efficiency and efficaciousness. The impetus for this surveillance evaluation project was chronic wasting disease (CWD) and the objectives were to apply both qualitative and quantitative methodologies to examine the components of CWD surveillance in Saskatchewan.<p>
A retrospective review of deer pathology and hunter-harvest submissions in Saskatchewan was conducted through the Canadian Cooperative Wildlife Health Centre. Qualitative evaluation methods outlined by Klauke et al (1988) were used and included key stakeholder interviews. A quantitative evaluation, with specific focus on disease detection, was conducted to examine system sensitivity, confidence of disease freedom and to compare system components using methods described by Martin et al (2007). The analysis was conducted using a scenario tree and Monte Carlo simulation.<p>
Sampling rates of dead and clinically ill deer were low with a high degree of variability by season, year, location and nature of submissions. Ultimately, variability of submission patterns likely affected when and where diseases were detected. Poor data quality reduced the amount of available data for analysis but quality dramatically improved over time.<p>
The surveillance evaluation demonstrated that the current surveillance system places more emphasis on monitoring trends in CWD-positive areas, at the expense of early detection. This is explained mostly by the coupling of disease control efforts and surveillance, in that harvests are heavily focused in CWD-positive areas. The system is not sufficient to detect disease in new areas where the disease prevalence is low, primarily due to low submission rates.<p>
The quantitative evaluation found that overall sensitivity of the surveillance system and confidence of disease freedom was highly dependent on detection prevalence and the ongoing risk of disease introduction. Surveillance in the eastern part of Saskatchewan was not adequate from 1997-2006 to detect CWD at 0.5-1% prevalence. However, if risk of CWD introduction over this time period was assumed to be low, it can be concluded that the prevalence in this region was not 5% or higher.<p>
A detection goal of 0.5-1% prevalence is an ambitious surveillance goal, especially in areas where the risk of disease introduction is high. The use of more targeted surveillance strategies should be further explored to help better meet surveillance these surveillance objectives.
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An evaluation of the long-term treatment outcomes of a multidisciplinary chronic pain centre programWagner, Flo 21 December 2009
The Chronic Pain Center (CPC) in Saskatoon offers a multidisciplinary treatment program whose goals are to facilitate improved coping skills, function and well-being, and to promote self-reliant lifestyles. They have documented a statistically significant improvement on several measures of physical and social functioning at the completion of the six week program, but to date have no formal evaluation of the long term effects.<p/>
The purpose of this study was to re-evaluate the CPC clients (treatment group) at least one year following their completion of the treatment program to determine if they had maintained those improvements and also to compare them to the group of clients (control group) who underwent initial multidisciplinary assessment at the Centre, but did not attend the six week treatment program. Evaluation by mail out questionnaires assessed several important aspects of chronic pain. A 34% response rate resulted in 142 participants for this study.<p/>
Data analyses involved a multi-stage process of univariate, bivariate and multivariate analyses. For the first goal, evaluating changes in the treatment group over time, the outcome variables considered had been administered at three points in time: admission to the CPC program, discharge from the six week program, and at study follow-up. For the second goal, the treatment and control groups were compared at one point in time; the study follow-up.<p/>
The study demonstrated that the scores on all outcome variables used in the follow-up study improved significantly from the time of assessment to the time of discharge for the clients who attended the CPC treatment program. These improvements declined over time, but remained significantly improved from the admission scores. (Wilks Ë=.501, F(1,48)=4.788, p=.000) However, the study was unable to demonstrate any significant differences between the treatment and control groups on any of the outcome measures at the time of the study follow-up.(Wilks Ë=.930, F (1,107) = 1.014, p=.430) There were several limitations to this study, including the use of a non-randomized control group and the method of recruitment, which may have introduced bias into the study and affected the ability to effectively explain this finding.<p/>
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Living with a Chronic Illness in Adolescence and Emerging AdulthoodSnelgrove, Ryan January 2012 (has links)
This study explored the lived experiences of chronic illness during adolescence and emerging adulthood. Previous research has indicated that chronic illness can result in disruptions to people’s lives because of the related physical challenges and social stigmas. These challenges may be particularly salient in adolescence and emerging adulthood because of pressure to “fit in” with peers, cultural associations between youth and health, and limited experience adjusting to difficult life events. However, little is known about the impact of having a chronic illness on the lives of young people. This study addresses the over-arching question: how and when can chronic illness become a problem for young people in their everyday lives (i.e., leisure, relationships, school and work) and what types of adjustments are made as a result? The final sample of participants in this study consisted of 29 young people (23 women, 6 men) each of whom was living with a chronic illness. Unstructured in-depth interviews were conducted with 26 participants, as well as 3 semi-structured electronic interviews. Data were analyzed using a grounded theory approach. The findings suggested that the main challenge for young people with illness is achieving a desired identity. Being able to achieve a desired identity was tied to three processes. These processes included participants’ ability to manage their appearances and reputations, accomplish desired activities, and experience positive relationships. Although most adolescents and emerging adults to some degree face these same challenges in attempting to achieve desired identities, experiences associated with chronic illness can intensify these challenges. Further, the factors that contribute to them being challenging seem to be unique to those living with a chronic illness. The findings also suggested that participants’ experienced chronic illness in varied ways. Many of the adjustments and factors that contributed to these differences, including how people’s experiences changed over time are identified. These adjustments and factors are similar to the coping strategies and constraint negotiation strategies identified in previous research at a generic level. The specific ways in which young people with chronic illness are able to achieve identity is also described, including differences within the experiences of participants.
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Correlation of MicroRNA Expressions with mutated and unmutated IgVH gene groups in chronic lymphocytic leukemiaZou, Yi 28 April 2005 (has links)
B-cell chronic lymphocytic leukemia is the most common leukemia in the adult population of Western developed countries. In 2005, an estimated 9,730 adults in the United States will be diagnosed with B-CLL and an estimated 4,600 deaths will occur. B-CLL is a common heterogeneous malignant disease with variable outcome. B-CLL is divided into two groups based on whether somatic hypermutation is observed in the variable region of the immunoglobulin heavy-chain locus (IgVH). The two distinct groups are named mutated and unmutated. The B-CLL mutated group has a more favorable prognosis than the unmutated group.
Gene expression profiling has been used successfully to decipher the biological and clinical diversity of many leukemias and lymphomas. Recently, other small RNAs (microRNAs) have been shown to be important in hematopoiesis. MicroRNAs are small 20-28 nucleotide RNAs that are believed to control many important cellular and developmental processes by posttranscriptional gene silencing, translational repression, and modulating epigenetic events.
We are interested in whether microRNA expression correlates with the mutational status of IgVH. This study is significant in the following ways: (1) microRNAs may become surrogate markers for the mutational status of IgVH of B-CLL, which implies a more rapid diagnostic means as compared to the current practice, and (2) microRNAs, in the particular context of B-CLL, may play some significant roles in a gene regulatory network that is further responsible for chromosomal abnormalities found in B-CLL.
This thesis presents a study comparing microRNA expression in mutated and unmutated B-CLL groups. Instead of using a genome-wide expression profiling strategy, we selected a specific set of microRNAs based on their chromosome locations and mRNA targets. Specifically, we chose the following eight microRNAs (with their chromosomal abnormalities): mir16-1 (deletion 13), let-7i (trisomy 12), mir196-2 (trisomy 12), mir26a-2 (trisomy 12), mir-34b (deletion 11), mir-125b (deletion 11), mir-181C (trisomy 19), mir-125a (trisomy 19). We used solution hybridization assays to monitor the expression of microRNAs. We successfully characterized the microRNA expression in twelve B-CLL patient samples (eight mutated and four unmutated). Among the eight microRNAs examined, three (mir196-2, mir-125a, mir-125b) are not expressed in the two B-CLL groups, four (mir16-1, mir26a-2, let-7i, mir-34b) have significant differences in expressions over the two groups, and one (mir-181c) has no significant difference in expressions over the two groups.
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Framing chronic illness : fatigue syndromes, metaphor and meaningBowditch, Joanne R. 15 April 2006 (has links)
Fibromyalgia Syndrome (FMS) and Chronic Fatigue Immune Dysfunction Syndrome (CFIDS) are primarily womens syndromes. Both syndromes are highly contested within the biomedical and scientific communities and within the general population. Because there is no apparent cause for the syndromes and no available treatment, women living with FMS and/or CFIDS must live with difficult and disabling symptoms. <p>This research also analyzes the metaphors used in the scientific and biomedical literature to describe the same symptoms as listed above. A comparison is drawn between this analysis and that focused on the womens use of metaphors. It is found that although many of the metaphors are the same, they differ in discursive employment. Environmental metaphors, along with metaphors of fracture, harm and productivity are used by the research participants with a very different intent than how the same metaphors are used in the biomedical literature. The women used the metaphors to reveal the ways in which their symptoms are influenced by the social and cultural forces in their everyday lives. The biomedical and scientific use of metaphors reinforced the highly contested view that the symptoms are influenced more by individual psychological and emotional deficiencies than by broader structural forces.
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Wildlife surveillance systems : chronic wasting diseaseTataryn, Joanne Rosemary 17 September 2009 (has links)
Increased demand for animal disease surveillance information has led to the development and refinement of methodologies for qualitative and quantitative surveillance system evaluations to maximize efficiency and efficaciousness. The impetus for this surveillance evaluation project was chronic wasting disease (CWD) and the objectives were to apply both qualitative and quantitative methodologies to examine the components of CWD surveillance in Saskatchewan.<p>
A retrospective review of deer pathology and hunter-harvest submissions in Saskatchewan was conducted through the Canadian Cooperative Wildlife Health Centre. Qualitative evaluation methods outlined by Klauke et al (1988) were used and included key stakeholder interviews. A quantitative evaluation, with specific focus on disease detection, was conducted to examine system sensitivity, confidence of disease freedom and to compare system components using methods described by Martin et al (2007). The analysis was conducted using a scenario tree and Monte Carlo simulation.<p>
Sampling rates of dead and clinically ill deer were low with a high degree of variability by season, year, location and nature of submissions. Ultimately, variability of submission patterns likely affected when and where diseases were detected. Poor data quality reduced the amount of available data for analysis but quality dramatically improved over time.<p>
The surveillance evaluation demonstrated that the current surveillance system places more emphasis on monitoring trends in CWD-positive areas, at the expense of early detection. This is explained mostly by the coupling of disease control efforts and surveillance, in that harvests are heavily focused in CWD-positive areas. The system is not sufficient to detect disease in new areas where the disease prevalence is low, primarily due to low submission rates.<p>
The quantitative evaluation found that overall sensitivity of the surveillance system and confidence of disease freedom was highly dependent on detection prevalence and the ongoing risk of disease introduction. Surveillance in the eastern part of Saskatchewan was not adequate from 1997-2006 to detect CWD at 0.5-1% prevalence. However, if risk of CWD introduction over this time period was assumed to be low, it can be concluded that the prevalence in this region was not 5% or higher.<p>
A detection goal of 0.5-1% prevalence is an ambitious surveillance goal, especially in areas where the risk of disease introduction is high. The use of more targeted surveillance strategies should be further explored to help better meet surveillance these surveillance objectives.
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360 |
An evaluation of the long-term treatment outcomes of a multidisciplinary chronic pain centre programWagner, Flo 21 December 2009 (has links)
The Chronic Pain Center (CPC) in Saskatoon offers a multidisciplinary treatment program whose goals are to facilitate improved coping skills, function and well-being, and to promote self-reliant lifestyles. They have documented a statistically significant improvement on several measures of physical and social functioning at the completion of the six week program, but to date have no formal evaluation of the long term effects.<p/>
The purpose of this study was to re-evaluate the CPC clients (treatment group) at least one year following their completion of the treatment program to determine if they had maintained those improvements and also to compare them to the group of clients (control group) who underwent initial multidisciplinary assessment at the Centre, but did not attend the six week treatment program. Evaluation by mail out questionnaires assessed several important aspects of chronic pain. A 34% response rate resulted in 142 participants for this study.<p/>
Data analyses involved a multi-stage process of univariate, bivariate and multivariate analyses. For the first goal, evaluating changes in the treatment group over time, the outcome variables considered had been administered at three points in time: admission to the CPC program, discharge from the six week program, and at study follow-up. For the second goal, the treatment and control groups were compared at one point in time; the study follow-up.<p/>
The study demonstrated that the scores on all outcome variables used in the follow-up study improved significantly from the time of assessment to the time of discharge for the clients who attended the CPC treatment program. These improvements declined over time, but remained significantly improved from the admission scores. (Wilks Ë=.501, F(1,48)=4.788, p=.000) However, the study was unable to demonstrate any significant differences between the treatment and control groups on any of the outcome measures at the time of the study follow-up.(Wilks Ë=.930, F (1,107) = 1.014, p=.430) There were several limitations to this study, including the use of a non-randomized control group and the method of recruitment, which may have introduced bias into the study and affected the ability to effectively explain this finding.<p/>
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