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The purpose of this mixed methods study was to understand how context may shape multiple goal negotiation. Prior research has focused on identifying variables that influence goal pursuit in general, but little attention has been given to how these principles operate in different circumstances. This study adopted the Dynamic Systems Model of Role-Identity and studied context through an identity lens. The context of the L2 teacher was selected as the focus of investigation, specifically the L2 teacher's pursuit of speaking in the second language for 90% of instructional time while forming meaningful relationships with students. Fifty six L2 teachers participated. The study was carried out over five phases. In the first phase, data were collected in an online survey targeting teachers' contextual variables, goal commitment, goal expectancy, self-accordance, job satisfaction, and perception of goal conflict. In the second phase, teachers were divided into groups based on their perception of conflict between the two goals: misaligned, no effect, and aligned. Chi-square analysis and Fischer exact tests were conducted and the only significant difference between groups was the amount of L2 spoken. A MANOVA, followed by univariate analysis found that the groups differed significantly regarding their level of commitment to the L2 goal, and their goal expectancy for forming relationships. In the third phase, a content analysis of the open-ended responses found that context influenced the goal navigation process, that the most frequent approach to resolving conflict was abandoning the L2 goal, that multifinality is contingent on one's role-identity, and that tension may be conscious or unconscious. In the fourth phase, 14 L2 teachers completed semi-structured interviews, which were used to further explore how role-identity informs goal navigation. Analysis of the transcripts revealed that role-identity has a powerful influence on how teachers manage and construal their goals. In the fifth and final phase, all the data were synthesized, resulting in the implications for researchers, administrators, and teachers. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]

Biocatalytic imine reductions and reductive aminations are an important tool to access high value primary, secondary, and tertiary chiral amines. Chiral amines are a prevalent functional group that is found in around 40% of pharmaceuticals and 20% of agrochemicals. Imine reductases, and the more recently discovered reductive aminases, are two valuable classes of biocatalysts that have emerged in recent years. They both possess a wide substrate scope of ketones and amines, therefore making them suitable candidates for reductive aminations, as well as a wide scope of imines for imine reductions. Despite the promise that these two enzymes show over other relevant biocatalysts for accessing chiral amines such as transaminases and monoamine oxidases, IREDs and RedAms have their limitations. The activity and stereoselectivity of these enzymes have been shown to be very substrate dependent. Even small changes in substituents, e.g. in steric demands or electronic properties, can result in drastically reduced, or improved, activity, as well as invert the enantiopreference. This report looks at exploring the activity and stereoselectivity of a reductive aminase from Ajellomyces dermatitidis (AdRedAm) towards previously untested carbonyl acceptors that showed interest as pharmaceutical building block precursors. Of the 7 carbonyl acceptors chosen for investigation, only one showed conversion to the desired amine product which was 1-methylpiperidine-2,3-dione. This achieved conversions of up to 80% and 78.6% with allylamine and trifluoroethylamine as the amine donors respectively. A secondary peak in GC traces was observed with this reactions which corresponding to the intermediate enamine compound that formed through tautomerization after the in situ formation of the imine intermediate. Through enzyme and no enzyme control reactions it was observed that this in situ imine formation and enamine tautomerization was not enzyme catalysed and reach 100% conversion to the enamine after 1 hour. The poor feasibility of the chosen substrates as carbonyl acceptors for reductive amination lead to a rational engineering investigation into a selection of active site residues. A total of six residues (N93, Y177, W208, H215, M237, and Q238) were selected in AdRedAm based on crystallographic data previously obtained from the reductive aminase from Aspergillus oryzae (AspRedAm)90 and screed against 2-phenylpyrroline and other cyclic imines with an aromatic substituent in the 2-position. Of the seven variants generated, W208A and M237G stood out as the best performing due to showing either an improvement in activity or stereoselectivity, or an inversion in stereoselectivity. AdWT showed a conversion of 19% for 2-phenylpyrroline and was 92% (S)-selective whereas W208A and M237G showed conversions of 100% and 54% with ee values of >99% (S) and 88% (R) respectively. Addition of a para-chloro group onto the aromatic resulted in a change of stereoselectivity of AdWT, N94A, Y177F, and H215A to the (R)-enantiomer. This substrate was more accepted by AdWT with conversion of 39% to the amine after 3 hours. W208A and M237G showed conversions of 99% and 25% with ee values of 74% (S) and 88% (R) respectively. A para-methoxy substituent on the aromatic ring resulted in 99% conversion and was >99% (S)-selective. Upon changing the ring size to a 6-membered ring, W208A and M237G both showed 100% conversion and ee >99% (R) compared to the AdWT with a conversion of 30% and 72% (R)-selective. This shows that the stereoselectivity of this reductive aminase is also substrate dependent as well as the shape and chemical nature of the active site. An in-silico docking was carried out of 2-phenylpyrroline into AspWT as well as the corresponding mutations of W208A and M237G from AdRedAm (W210A and M239G). It was seen in both variants, a domain shift around positions 238 and 239 had occurred which appears to push the substrate closer to the cofactor, resulting in a faster turnover of the substrate. It can also be seen in both variants that the phenyl group is oriented in the same direction however, a different face of the imine is adjacent to the transferred hydride from the cofactor in each model explaining the inversion in stereoselectivity. W208A was chosen for testing for the reductive amination between different carbonyls with aniline and substituted anilines due to its excellent conversions the imine reduction of different cyclic imines. AdWT showed reductive amination activity between cyclohexanone and aniline at a 1:1 ratio, however 56% of the amine product was see when W208A was used instead. This value dropped for different carbonyl ring sizes with aniline with cyclopentanone and cycloheptanone showing conversions of 16% and 3.2% respectively. Open chain carbonyls were less accepted than cyclic carbonyls with conversions seen of 16%, 8%, and 4% for the reductive amination between aniline and 2-heptanone, 2-hexanone, and 2-pentanone respectively. Benzaldehyde was a far better carbonyl acceptor for aniline with conversion to the secondary amine product >99%. When looking at different substituents on aniline, cyclohexanone was chosen as the carbonyl acceptor. Steric crowding around the reaction centre (near the nitrogen of aniline) was unflavoured with para-methyl, meta-methyl, and ortho-methyl giving conversion of 19%, 9.7%, and 0% respectively. Electron donating substituents were more favoured than electron withdrawing with para-methoxy and para-chloro giving the amine in 42.4% and 22% and para-fluorine and a para-nitro group having conversions of 5.3% and 0%. We have shown that through single point mutations of a reductive aminase, activity towards both imine reduction and reductive amination can be drastically improved on as well as a level of control over stereoselectivity for some substrates.

Community services are fundamental in the delivery of health care, providing local care close to or in patient homes. However, planning, managing and evaluating these services can be difficult. One stand out challenge is how these services may be organised to provide coordinated care given their physical distribution, patients using multiple services, and the increasing use of these services by patients with differing needs. This is complicated by a lack of comparable measures for evaluating quality across differing community services. Presented in this thesis is work that I conducted, alongside the North East London Foundation Trust, to understand referrals and the use of outcome data within community services through data visualisation and mathematical modelling. Firstly, I applied several data visualisations, building from a network analysis, to aid the design of a single point of access for referrals into community services - helping to understand patterns of referrals and patient use. Of interest were concurrent uses of services, whether common patterns existed and how multiple referrals occurred over time. This highlighted important dynamics to consider in modelling these services. Secondly, I developed a patient flow model, extending fluid and diffusion approximations of stochastic queueing systems to include complex flow dynamics such as re-entrant patients and the use of multiple services in sequence. Patient health is also incorporated into the model by using states that patients may move between throughout their care, which are used to model the differential impact of care. I also produced novel methods for allocating servers across parallel queues and patient groups. Finally, I developed the concept of ``the flow of outcomes'' - a measure of how individual services contribute to the output of patients in certain health states over time - to provide operational and clinical insight into the performance of a network of services.

There is a severe shortage of rural physicians in America. One reason physicians choose not to practice, or persist in practice, in rural areas is due to a lack of professional community, i.e., community of practice (CoP). Online, "virtual" CoPs, enabled by now common Internet communication technology can help give rural physicians the CoP experience they traditionally have lacked, despite their remote practice locations. Therefore, it is important for rural medical education programs to provide technological experiences that give students the skills needed to create virtual CoPs in future rural practice contexts. The Oregon Rural Scholars Program (ORSP) provides such a technological experience in the form of the Student Clinical Round (SCR) activity. ORSP students located in remote, rural parts of Oregon "meet" in a synchronous online space (i.e., a virtual meeting room) with a faculty member, where they participate in the SCR activity via video chat, screen and document sharing, real-time collaborative note taking, and text chatting. The literature indicates that activities like the SCR may be precursors to virtual CoPs, and therefore it is important to better understand the ORSP SCR as it could be a strategy for creating virtual CoPs among rural practitioners. As the ORSP SCR is a novel educational approach among U.S. rural medical education programs, an intrinsic case study design was used to explore the impact of the SCR activity on one cohort of ORSP third-year medical students. Additionally, the study sought to better understand the nature of the ORSP students' experiences of having participated in the SCR. Recorded SCR sessions were coded using the Community of Inquiry (CoI) framework, a well validated methodology for analyzing higher education online learning. The CoI analysis revealed a movement of the group away from an individual, task focus towards a community, collaborative focus as the SCR sessions progressed. Additionally, student interview and field notes analyses revealed that the SCR experience reduced isolation, increased sense of community and positively influenced rural practice choice among the study participants. Conclusions drawn from this study are that the online ORSP SCR experience provides a strong social constructivist learning environment, thus creating the context for virtual CoP emergence. Additionally, the SCR activity is capable of generating an actual virtual CoP, an event directly observed during the study. Recommendations call for rural medical education programs as well as current rural practitioners to adopt similar online approaches to group learning, as such approaches may provide contexts for virtual CoP formation, thus contributing to the likelihood future physicians may become and current physicians may persist as rural practitioners. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]