Synthetic approaches to syn-diol containing biologically active compounds /

The deoxy derivative of pancratistatin 1.10 was prepared in good yield through the use of a [4+2] Diels-Alder cycloaddition and Bischler-Napieralski cyclization approach. The Bischler-Napieralski cyclization was shown to yield two additional side products 2.9, 2.10, however, under slightly modified hydrolysis conditions, the tetracyclic product 2.11 was obtained exclusively in greater than 84% yield. Initial screening of the di-hydroxylatgd derivative, and the other complementary pair analogue 1.10' previously prepared in our laboratories gave interesting results. Both of these compounds were shown to exhibit cytostatic activity; the mono-alcohol was marginally active while the di-hydroxylated analogue proved to be more potent although one to two magnitudes less potent than pancratistatin itself Human tumour cell line assay results indicated that the di-hydroxylated derivative exhibited selective cytotoxic inhibition in the following cell lines: non-small cell lung cancer line NCI-H226 (ED50 - 0.65 ^g/mL), leukemia cell lines CCRF-CEM (ED30 = 0.55 Hg/mL) and HL-60(TB) (ED50 = 0.89^ig/mL). Our results demonstrated that the pharmacophore is not a mono-alcohol, and that the minimum pharmacophore contains the hydroxyl group at the C4 position in addition to either, or both, of the hydroxyl groups present at C2 and C3.' The minimum pharmacophore has been narrowed to only three possibilities which are current synthetic targets in several research groups. The controlled Grignard addition to the tartaric acid derived bis-Weinreb amide 1.25 afforded a direct entry to a host of 1,4-diflferentiated tartaric acid derived intermediates (2.12-2.18). This potentially usefiil methodology was demonstrated through the efficient synthesis of the naturally occurring lactone 2.23, which bears the inherent syn-dio\ subunit. Based on this result, a similar approach to the synthesis of syn-dio\ bearing natural products looks very promising? A direct 2,3-diol desymmetrization method using TIPS-triflate was shown to be effective on the selective differentiation of Z,-methyl tartrate (and diisopropyl tartrate). The mono-silyl-protected intermediates 2.31 also proved to be useful when they were selectively differentiated at the 1,4-carboxyl position (2.35, 2.36) through the use of a borohydride reducing agent. Furthermore, the mono-silyl-protected derivative underwent periodate cleavage affording two synthetically useful a,P-unsaturated esters 2.43, 2.44, with one of esters being obtained via a silyl-migration method.''

Implementing the OPTIMAL model : the impact on students' motivation in an elementary school games environment

Optimal challenge occurs when an individual perceives the challenge of the task to be equaled or matched by his or her own skill level (Csikszentmihalyi, 1990). The purpose of this study was to test the impact of the OPTIMAL model on physical education students' motivation and perceptions of optimal challenge across four games categories (i. e. target, batting/fielding, net/wall, invasion). Enjoyment, competence, student goal orientation and activity level were examined in relation to the OPTIMAL model. A total of 22 (17 M; 5 F) students and their parents provided informed consent to take part in the study and were taught four OPTIMAL lessons and four non-OPTIMAL lessons ranging across the four different games categories by their own teacher. All students completed the Task and Ego in Sport Questionnaire (TEOSQ; Duda & Whitehead, 1998), the Intrinsic Motivation Inventory (IMI; McAuley, Duncan, & Tanmien, 1987) and the Children's Perception of Optimal Challenge Instrument (CPOCI; Mandigo, 2001). Sixteen students (two each lesson) were observed by using the System for Observing Fitness Instruction Time tool (SOFTT; McKenzie, 2002). As well, they participated in a structured interview which took place after each lesson was completed. Quantitative results concluded that no overall significant difference was found in motivational outcomes when comparing OPTIMAL and non-OPTIMAL lessons. However, when the lessons were broken down into games categories, significant differences emerged. Levels of perceived competence were found to be higher in non-OPTIMAL batting/fielding lessons compared to OPTIMAL lessons, whereas levels of enjoyment and perceived competence were found to be higher in OPTIMAL invasion lessons in comparison to non-OPTIMAL invasion lessons. Qualitative results revealed significance in feehngs of skill/challenge balance, enjoyment and competence in the OPTIMAL lessons. Moreover, a significance of practically twice the active movement time percentage was found in OPTIMAL lessons in comparison to non-OPTIMAL lessons.

An exploration of the experience of implementing the second step violence prevention curriculum in one primary general learning disabilities class /

Violence has always been a part of the human experience, and therefore, a popular topic for research. It is a controversial issue, mostly because the possible sources of violent behaviour are so varied, encompassing both biological and environmental factors. However, very little disagreement is found regarding the severity of this societal problem. Most researchers agree that the number and intensity of aggressive acts among adults and children is growing. Not surprisingly, many educational policies, programs, and curricula have been developed to address this concern. The research favours programs which address the root causes of violence and seek to prevent rather than provide consequences for the undesirable behaviour. But what makes a violence prevention program effective? How should educators choose among the many curricula on the market? After reviewing the literature surrounding violence prevention programs and their effectiveness, The Second Step Violence Prevention Curriculum surfaced as unique in many ways. It was designed to address the root causes of violence in an active, student-centred way. Empathy training, anger management, interpersonal cognitive problem solving, and behavioural social skills form the basis of this program. Published in 1992, the program has been the topic of limited research, almost entirely carried out using quantitative methodologies.The purpose of this study was to understand what happens when the Second Step Violence Prevention Curriculum is implemented with a group of students and teachers. I was not seeking a statistical correlation between the frequency of violence and program delivery, as in most prior research. Rather, I wished to gain a deeper understanding of the impact ofthe program through the eyes of the participants. The Second Step Program was taught to a small, primary level, general learning disabilities class by a teacher and student teacher. Data were gathered using interviews with the teachers, personal observations, staff reports, and my own journal. Common themes across the four types of data collection emerged during the study, and these themes were isolated and explored for meaning. Findings indicate that the program does not offer a "quick fix" to this serious problem. However, several important discoveries were made. The teachers feU that the program was effective despite a lack of concrete evidence to support this claim. They used the Second Step strategies outside their actual instructional time and felt it made them better educators and disciplinarians. The students did not display a marked change in their behaviour during or after the program implementation, but they were better able to speak about their actions, the source of their aggression, and the alternatives which were available. Although they were not yet transferring their knowledge into positive action,a heightened awareness was evident. Finally, staff reports and my own journal led me to a deeper understanding ofhow perception frames reality. The perception that the program was working led everyone to feel more empowered when a violent incident occurred, and efforts were made to address the cause rather than merely to offer consequences. A general feeling that we were addressing the problem in a productive way was prevalent among the staff and students involved. The findings from this investigation have many implications for research and practice. Further study into the realm of violence prevention is greatly needed, using a balance of quantitative and qualitative methodologies. Such a serious problem can only be effectively addressed with a greater understanding of its complexities. This study also demonstrates the overall positive impact of the Second Step Violence Prevention Curriculum and, therefore, supports its continued use in our schools.

Exploring the experiences of male spousal caregivers for their wives with alzheimer disease in their homes : the lived experience and the men's perception of support groups /

This research is qualitative in nature and has explored, by means of interviews, the '^^ experiences of 10 men in their roles in caring for their spouses with Alzheimer Disease (see glossary) in their homes. Additional data were collected by attending 3 formal support group meetings and one informal meeting of a group of men who brought their wives to a support group meeting for their wives with AD. The data retrieved supported the assumption that education about the disease, utilization of formal community support services, and attendance at caregiver support groups or programs can assist healthy male caregivers in caring for their wives with AD in their homes.

Grade nine teachers' perception of how teachers, parents, peers, administrators, and community members affect the development of the grade nine student /

The purpose of this study was to examine grade nine teachers' perception of how teachers, parents, peers, administrators, and community members influence the overall development of grade nine students. Ten grade nine teachers (four male and six female) participated in the study which consisted of the completion of a one hour, tape-recorded interview. The central findings were as follows: 1) the grade nine student has evolved; 2) peers have an important impact on the four developmental areas (physical, emotional, social, and academic) of the grade nine student; and 3) the role of the grade nine teacher appears to have dramatically changed over the last seventeen years. Suggestions and recommendations for future research in this field are based on findings related to the enhancement of the secondary school experience for the grade nine adolescent.

Menstrual status and thermoregulatory responses of active adolescents during exercise in a cold environment

This study examined the interactions between the reproductive status and the thermoregulatory responses during exercise in the cold in girls involved in competitive sports. Four girls with established menstrual cycles comprised the eumenorrheic menarcheal group (EM) and 5 non-menstruating girls comprised the pre-menarcheal group (PM). During the first visit maximal oxygen consumption, height, weight and percent body fat (%BF) were measured. The second visit involved: a determination of metabolic rate in thermoneutrality (21°C) involving 10-min rest and 20-min cycling (30% of VCL max), and a cold stress test (5°C, 40% humidity, <0.3 m/s air velocity) involving 20-min rest and 40-min cycling (30% of VCL max.). Subjects in the EM group were tested twice in the chamber during the follicular and luteal phases. Pre-menarcheal subjects were found to have significantly (p<0.05) lower core temperatures during the final stages of cold exposure. Overall, body fat was not significantly correlated with core temperature in the cold, however there was a significant surface-to-mass ratio difference between the groups. While in the follicular phase, EM girls had a higher core temperature during cold exposure. Therefore, reproductive hormonal status seems to be an important factor in terms of cold tolerance in females during adolescence.

Physiological reactivity and the perception of emotional stimuli as they relate to social adaptive functioning after traumatic brain injury / y Melonie Jane Hopkins.

Traumatic brain injury (TBI) often affects social adaptive functioning and these changes in social adaptability are usually associated with general damage to the frontal cortex. Recent evidence suggests that certain neurons within the orbitofrontal cortex appear to be specialized for the processing of faces and facial expressions. The orbitofrontal cortex also appears to be involved in self-initiated somatic activation to emotionally-charged stimuli. According to Somatic Marker Theory (Damasio, 1994), the reduced physiological activation fails to provide an individual with appropriate somatic cues to personally-relevant stimuli and this, in turn, may result in maladaptive behaviour. Given the susceptibility of the orbitofrontal cortex in TBI, it was hypothesized that impaired perception and reactivity to socially-relevant information might be responsible for some of the social difficulties encountered after TBL Fifteen persons who sustained a moderate to severe brain injury were compared to age and education matched Control participants. In the first study, both groups were presented with photographs of models displaying the major emotions and either asked to identify the emotions or simply view the faces passively. In a second study, participants were asked to select cards from decks that varied in terms of how much money could be won or lost. Those decks with higher losses were considered to be high-risk decks. Electrodermal activity was measured concurrently in both situations. Relative to Controls, TBI participants were found to have difficulty identifying expressions of surprise, sadness, anger, and fear. TBI persons were also found to be under-reactive, as measured by electrodermal activity, while passively viewing slides of negative expressions. No group difference,in reactivity to high-risk card decks was observed. The ability to identify emotions in the face and electrodermal reactivity to faces and to high-risk decks in the card game were examined in relationship to social monitoring and empathy as described by family members or friends on the Brock Adaptive Functioning Questionnaire (BAFQ). Difficulties identifying negative expressions (i.e., sadness, anger, fear, and disgust) predicted problems in monitoring social situations. As well, a modest relationship was observed between hypo-arousal to negative faces and problems with social monitoring. Finally, hypo-arousal in the anticipation of risk during the card game related to problems in empathy. In summary, these data are consistent with the view that alterations in the ability to perceive emotional expressions in the face and the disruption in arousal to personally-relevant information may be accounting for some of the difficulties in social adaptation often observed in persons who have sustained a TBI. Furthermore, these data provide modest support for Damasio's Somatic Marker Theory in that physiological reactivity to socially-relevant information has some value in predicting social function. Therefore, the assessment of TBI persons, particularly those with adaptive behavioural problems, should be expanded to determine whether alterations in perception and reactivity to socially-relevant stimuli have occurred. When this is the case, rehabilitative strategies aimed more specifically at these difficulties should be considered.

From inference to affordance : the problem of visual depth-perception in the optical writings of Descartes, Berkeley, and Gibson

This thesis explores the debate and issues regarding the status of visual ;,iferellces in the optical writings of Rene Descartes, George Berkeley and James 1. Gibson. It gathers arguments from across their works and synthesizes an account of visual depthperception that accurately reflects the larger, metaphysical implications of their philosophical theories. Chapters 1 and 2 address the Cartesian and Berkelean theories of depth-perception, respectively. For Descartes and Berkeley the debate can be put in the following way: How is it possible that we experience objects as appearing outside of us, at various distances, if objects appear inside of us, in the representations of the individual's mind? Thus, the Descartes-Berkeley component of the debate takes place exclusively within a representationalist setting. Representational theories of depthperception are rooted in the scientific discovery that objects project a merely twodimensional patchwork of forms on the retina. I call this the "flat image" problem. This poses the problem of depth in terms of a difference between two- and three-dimensional orders (i.e., a gap to be bridged by one inferential procedure or another). Chapter 3 addresses Gibson's ecological response to the debate. Gibson argues that the perceiver cannot be flattened out into a passive, two-dimensional sensory surface. Perception is possible precisely because the body and the environment already have depth. Accordingly, the problem cannot be reduced to a gap between two- and threedimensional givens, a gap crossed with a projective geometry. The crucial difference is not one of a dimensional degree. Chapter 3 explores this theme and attempts to excavate the empirical and philosophical suppositions that lead Descartes and Berkeley to their respective theories of indirect perception. Gibson argues that the notion of visual inference, which is necessary to substantiate representational theories of indirect perception, is highly problematic. To elucidate this point, the thesis steps into the representationalist tradition, in order to show that problems that arise within it demand a tum toward Gibson's information-based doctrine of ecological specificity (which is to say, the theory of direct perception). Chapter 3 concludes with a careful examination of Gibsonian affordallces as the sole objects of direct perceptual experience. The final section provides an account of affordances that locates the moving, perceiving body at the heart of the experience of depth; an experience which emerges in the dynamical structures that cross the body and the world.

Preoperative education and its influence on perception of recovery for clients awaiting total hip and total knee replacement surgery /

The puqjose of this study was to examine the manner in which an inviting approach to a preoperative teaching and learning educational experience influenced the perception and subsequent recovery of clients who were awaiting total hip and total knee replacement surgery. An in-depth review of the internal and external factors that shape client perceptions was undertaken in this study. In addition, this study also explored whether or not the Prehab Program was preparing clients physically, socially, and psychologically for surgery. Data for this qualitative case study research were collected through preoperative interviews with 4 participants awaiting total hip replacement surgery and 1 participant awaiting total knee replacement surgery. Four postoperative interviews were conducted with the participants who had received total hip replacement surgery. The occupational therapist and physical therapist who were the coleaders of the Prehab Program at the time of this study were also interviewed. The results of this study suggest that while individuals may receive similar educational experiences, their perceptions of the manner in which they benefited from these experiences varied. This is illustrated in the research findings, which concluded that while clients benefited physically from the inviting approach used during the practical teaching session, not all clients perceived the psychological benefits of this practice session, especially clients with preexisting high levels of anxiety. In addition to increasing the understanding of the internal as well as external factors that influence the perceptions of clients, this study has also served as an opportunity for reflection on practice for the Prehab therapists and other healthcare educators.