Aryl hydroxamic acid analogues as potential therapeutic agents /

A new synthetic pathway to analogues of the aglucones of naturally occurring cyclic hydroxamic acids (2,4-dihydroxy-l,4-benzoxazin-3-ones) has been developed. The new pathway involves the coupling of substituted nitrophenols wdth /-propyl-abromo- O-methoxymethylglycolate. These materials were reductively cyclised to reveal the hydroxamic acid functionality. Removal of the C-2 0-methoxymethyl protecting group was achieved chemoselectively using boron trichloride. The analogue 7-methoxy-2,4-dihydroxy-l,4-benzoxazin-3-one (DIMBOA) was assayed with papain and a semilog plot of activity of papain in the presence of excess DIMBOA was found to be linear. A single exponential equation was suggested as the model for kinetic analysis. '^ Nuclear magnetic resonance (NMR) spectra of a couple of hydroxamates were acquired as reference standards for future mechanistic studies of these compounds as thiol protease inhibitors. A 10% '^-labeled sample ofDIMBOA was also prepared for future mechanistic studies using NMR techniques.

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.

Teaching Principled negotiation skills to parents and their children : the impact of parental involvement /

This study explored the impact of training parents and children concurrently in principled negotiation skills for the purpose of developing negotiation skills and problem solving abilities in children. A second experimental group was utilized to determine the viability of negotiation skills training of junior elementary students for the purpose of improving problem solving and conflict resolving abilities. The student population in each experimental group was trained using The Program for Young Negotiators (Curhan, 1996). A control group was also established using the remaining grade four and five students attending the participating school. These students did not receive training as part of this study. Student group distribution was as follows: Experimental group 1 (students with parent participant) consisted of 10 (5 grade five and 5 grade 4 students), Experimental group 2 students without parent participant) consisted of 48 (20 grade 4 and 28 grade 5 students), and the Control group 3 (55 grade 4 and 5 students). The impact of training was measured using the Five Factor Negotiation Scale developed for use with the Program for Young Negotiators (Curhan, 1996). This measure was employed as a pre- and post-test questionnaire to the total student population, (113 students) to determine levels of ability in each of the key elements of negotiation, personal initiative, collaboration, communication, conflict based perspective taking, and conflict resolution approach (Nakkula & Nikitopoulos, unpublished). This measure has a coefficient alpha of .75 which is acceptable for this type of affective instrument. As well, open ended ability questions designed to measure ability, knowledge, and behaviour as they relate to negotiation skill application were given to the total student population, (113 students). Finally, journals were maintained by the students in both experimental groups, and informal feedback discussions were held with students and parents participating in the study.The intent of using both qualitative and quantitative measures was to provide an overall perspective of student abilities as they related to principled negotiation skills. While the quantitative measures were from the student perspective, more qualitative information was sought from parents and teachers through informal interviews, discussions, and use of confidential feedback cards. For analysis purposes, the ability questions were randomly selected for Experimental group 2 and Control group 3 in an effort to balance the groups more equitably with Experimental group 1. The findings of this study indicate that students of the junior elementary school age can be taught how to perceive conflict in a more constructive way. However, they are not as likely to use their skills when the conflict is with a sibling as they are with a peer, a teacher, or a parent. While no statistically significant differences between mean scores for Experimental groups 1 and 2 exist some subtle differences are noted. Overall, increases in mean scores for grade 4 students exceeded the increases for grade 5 students within Experimental group 1 . The implication being that younger students benefit more from having a parent trained in principled negoUation skills than older students. The skill level of a parent in principled negotiation can not be underesUmated. Without a consistent and effective role model the likelihood of developing student skill level to a point of automaticity is greatly reduced. Enough so that perhaps the emphasis should be placed on training parents more so than the students.

Carbohydrate refeeding rapidly reverses the adaptive upregulation of human skeletal muscle pyruvate dehydrogenase kinase following a high fat diet

The time course for the reversal of the adaptive increase in pyruvate dehydrogenase kinase (PDK) activity following a 6d high fat diet (HP: 4.2 ± 0.2 % carbohydrate; 75.6 ± 0.4 % fat; 19.5 ± 0.8 % protein) was investigated in human skeletal muscle (vastus lateralis). HF feeding increased PDK activity by 44% (from 0.081 ± 0.025 min"' to 0.247 ± 0.025 mm\p < 0.05). Following carbohydrate re-feeding, (88% carbohydrate; 5% fat; 7% protein), PDK activity had returned to baseline (0.111 ± 0.014 min"') within 3h of re-feeding. The active fraction of pyruvate dehydrognease (PDHa) was depressed following 6d of the HF diet (from 0.89 ± 0.21 mmol/min/kg WW to 0.32 ± 0.05 mmol/min/kg ww,p <0.05) and increased to pre-HF levels by 45 min of post re-feeding (0.74 ±0.19 mmol/min/kg ww) and remained elevated for 3h. Western blotting analysis of the PDK isoforms, PDK4 and PDK2, revealed a 31% increase in PDK4 protein content following the HF diet, with no change in PDK2 protein. This adaptive increase in PDK4 protein content was reversed with carbohydrate re-feeding. It was concluded that the adaptive up-regulation in PDK activity and PDK4 protein content was fiilly reversed by 3h following carbohydrate re-feeding.

Analysis of the late correspondence between our administration and Great Britain & France, with an attempt to show what are the real causes of the failure of the negotiation.

Ten pieces originally published in the Columbian Centinel. A later edition with imprint New York, Printed for E. Sargeant, 1809, contains two additional pieces.

The practical application of a meta-analysis of deinstitutionalization : adaptive behaviour outcomes and the piloting of a transitional questionnaire for adults with intellectual disabilities

This investigation examined the effects of de institutionalization on the adaptive behaviour and adjustment of adults with intellectual disabilities (ID). In study 1, a meta-analysis was conducted with 23 studies on deinstitutionalization adaptive behaviour outcomes. Deinstitutionalization was associated with modest improvements in adaptive behaviour however outcomes varied across adaptive behaviour domains and other substantive variables. Clinical and service implications of these results were explicated. Noting the trends from the meta-analysis, study 2 used this information in refining and piloting an Agency Transition Survey used to evaluate community transitions for persons with ID. Information derived from the survey was found to be valuable and adequate for the effective evaluation of transitional success. Potential applications of the survey and meta-analysis results were illustrated.

Thoughts upon the conduct of our administration in relation both to Great Britain and France, more especially in reference to the late negotiation, concerning the attack on the Chesapeake

Printed at the Repertory Office

Identity Formation and Negotiation of Afghan Female Youth in Ontario

The following thesis provides an empirical case study in which a group of 6 first generation female Afghan Canadian youth is studied to determine their identity negotiation and development processes in everyday experiences. This process is investigated across different contexts of home, school, and the community. In terms of schooling experiences, 2 participants each are selected representing public, Islamic, and Catholic schools in Southern Ontario. This study employs feminist research methods and is analyzed through a convergence of critical race theory (critical race feminism), youth development theory, and feminist theory. Participant experiences reveal issues of racism, discrimination, and bias within schooling (public, Catholic) systems. Within these contexts, participants suppress their identities or are exposed to negative experiences based on their ethnic or religious identification. Students in Islamic schools experience support for a more positive ethnic and religious identity. Home and community provided nurturing contexts where participants are able to reaffirm and develop a positive overall identity.

Deinstitutionalization and its Effects on Social Inclusion, Choice-Making, Adaptive and Maladaptive Behavior for Individuals with Intellectual Disabilities: Case Studies Analysis

In the past three decades institutions for persons with intellectual disabilities (ID) have been downsizing and closing in Ontario, Canada. This trend is reflective of the changes that have occurred in society. As of March 2009 the last institution operated by the Ontario government for persons with ID closed, placing the remaining approximately 1000 persons into the community. The current study was an analysis of part of one study in a four-study research project, called the Facilities Initiative Study, to explore the impact of the closures on the lives of individuals who have been reintegrated into community settings. The goal of the current case study analysis was to describe the impact of changes in social inclusion, choice-making/autonomy, and adaptive/maladaptive functioning of four individuals prior to and following transition to the community. The results suggested that, in most cases, community integration was related to more social inclusion opportunities and autonomy in choice-making, a wider range of adaptive behaviors and fewer maladaptive behaviors. In some cases, the evidence suggested that some of these indices of quality of life were not improving. Overall, the study found that the differences observed were unique to each of the individuals who participated in the case study analysis. Some generalized themes were generated that can be applied to future deinstitutionalization endeavors.

Assessing the adaptive capacity of the Ontario wine industry to climate change: A case study

The global wine industry is experiencing the impacts of climate change. Canada’s major wine sector, the Ontario Wine Industry (OWI) is no exception to this trend. Warmer winter and summer temperatures are affecting wine production. The industry needs to adapt to these challenges, but their capacity for this is unclear. To date, only a limited number of studies exist regarding the adaptive capacity of the wine industry to climate change. Accordingly, this study developed an adaptive capacity assessment framework for the wine industry. The OWI became the case study for the implementation of the assessment framework. Data was obtained by means of a questionnaire sent to grape growers, winemakers and supporting institutions in Ontario. The results indicated the OWI has adaptive capacity capabilities in financial, institutional, political, technological, perceptions, knowledge, diversity and social capital resources areas. Based on the OWI case study, this framework provides an effective means of assessing regional wine industries’ capacity to adapt to climate change.

Bargaining Power Dynamics and the Negotiation of Commercial Rights and Obligations: A Case of Athlete Agreements

This qualitative case study explored how the structural power imbalance in high performance sport influenced the bargaining process and resulting commercial rights and obligations of a single Canadian national sport organization’s (NSO1) Athlete Agreement. Principles comprising the doctrine of unconscionability, specifically the identification of a power imbalance between contracting parties, and the exploration of how that power imbalance influenced the terms of the contract, provided a framework to analyze factors influencing the commercial contents of NSO1’s Athlete Agreement. The results of this analysis revealed that despite the overarching influence of the inherent structural power imbalance on all aspects of NSO1 and its membership, an athletes’ level of commercial appeal can reach such heights as to balance the bargaining positions of both parties and subsequently influence the commercial contents of the Athlete Agreement.

Fit For Action: A Comparative Case Study of the Implementation of an Adaptive Fitness and Conditioning Program for Moderate Functioning Teens and Transition Age Youth with ASD

The purpose of my research was to develop and refine pedagogic approaches, and establish fitness baselines to adapt fitness and conditioning programs for Moderate-functioning ASD individuals. I conducted a seven-week study with two teens and two trainers. The trainers implemented individualized fitness and conditioning programs that I developed. I conducted pre and post fitness baselines for each teen, a pre and post study interview with the trainers, and recorded semi-structured observations during each session. I used multi-level, within-case and across case analyses, working inductively and deductively. My findings indicated that fundamental movement concepts can be used to establish fitness baselines and develop individualized fitness programs. I tracked and evaluated progressions and improvements using conventional measurements applied to unconventional movements. This process contributed to understanding and making relevant modifications to activities as effective pedagogic strategies for my trainers. Further research should investigate fitness and conditioning programs with lower functioning ASD individuals.

Novel Magnetic Materials Based on Macrocyclic Ligands: Towards High Relaxivity Contrast Agents and Mononuclear Single-Molecule Magnets

The preparation and characterization of coordination complexes of Schiff-base and crown ether macrocycles is presented, for application as contrast agents for magnetic resonance imaging, Project 1; and single-molecule magnets (SMMs), Projects 2 and 3. In Project 1, a family of eight Mn(II) and Gd(III) complexes of N3X2 (X = NH, O) and N3O3 Schiff-base macrocycles were synthesized, characterized, and evaluated as potential contrast agents for MRI. In vitro and in vivo (rodent) studies indicate that the studied complexes display efficient contrast behaviour, negligible toxicity, and rapid excretion. In Project 2, DyIII complexes of Schiff-base macrocycles were prepared with a view to developing a new family of mononuclear Ln-SMMs with pseudo-D5h geometries. Each complex displayed slow relaxation of magnetization, with magnetically-derived energy barriers in the range Ueff = 4 – 24 K. In Project 3, coordination complexes of selected later lanthanides with various crown ether ligands were synthesized. Two families of complexes were structurally and magnetically analyzed: ‘axial’ or sandwich-type complexes based on 12-crown-4 and 15-crown-5; and ‘equatorial’ complexes based on 18-crown-6. Magnetic data are supported by ab initio calculations and luminescence measurements. Significantly, the first mononuclear Ln-SMM prepared from a crown ether ligand is described.