It's all about relationships : A qualitative study of family physicians' teaching experiences in rural longitudinal clerkships.

INTRODUCTION: The relationship between preceptor and trainee is becoming recognized as a critical component of teaching, in particular in the negotiation of feedback and in the formation of professional identity. This paper elaborates on the nature of the relationships between preceptor and student that evolve in the context of rural longitudinal integrated clerkships (LICs). METHODS: We drew on constructivist grounded theory for the research approach. We interviewed nine LIC family practice preceptors from three sites at one educational institution. We adapted the interview framework based on early findings. We analyzed the data through a constant comparative process. We then drew on concepts of relationship-based learning as sensitizing concepts in a secondary analysis. RESULTS: We constructed three themes from the data. First, preceptors developed trusting professional and personal relationships with students over time. These relationships expanded to include friendship, advocacy, and ongoing contact beyond the clerkship year. Second, preceptors' approach to teaching was anchored in the relationship with an understanding of the individual student. Third, preceptors set learning goals collaboratively with their students, based not only on program objectives, but also with the student as a future physician in mind. DISCUSSION: Our findings suggest that rural family medicine preceptors developed engaged and trusting relationships with their students over time. These relationships imbued all activities of teaching and learning with an individual and personal focus. This orientation may be a key factor in supporting the learning outcomes demonstrated for students studying in rural LICs.

Driving external chemistry optimization via operations management principles.

Confronted with the need to significantly raise the productivity of remotely located chemistry CROs Pfizer embraced a commitment to continuous improvement which leveraged the tools from both Lean Six Sigma and queue management theory to deliver positive measurable outcomes. During 2012 cycle times were reduced by 48% by optimization of the work in progress and conducting a detailed workflow analysis to identify and address pinch points. Compound flow was increased by 29% by optimizing the request process and de-risking the chemistry. Underpinning both achievements was the development of close working relationships and productive communications between Pfizer and CRO chemists.

"I am a doctor": negotiating the discourses of standardization and diversity in professional identity construction.

PURPOSE: Medical educators have expressed concern that students' professional identities do not always align with their expectations or with professional standards. The authors propose that, in constructing appropriate professional identities, medical students today are affected by the competing discourses of diversity and standardization. METHOD: Between March and May 2012, the authors conducted a critical review of seminal publications to highlight the discourses of diversity and standardization in the medical education literature. They surveyed the social sciences literature on identity construction and drew examples from medical education to demonstrate how a social constructionist approach could inform the discussion about how medical students' professional identities are affected by these discourses. RESULTS: The discourse of diversity emphasizes individuality, difference, and a plurality of possibilities and advances the notion that heterogeneity is beneficial to medical education and to patients. In contrast, the discourse of standardization strives for homogeneity, sameness, and a limited range of possibilities and conveys that there is a single way to be a competent, professional physician. Thus, these discourses are in tension, a fact that medical educators largely have ignored. A social constructionist approach to identity suggests that medical students resolve this tension in different ways and construct different identities as a result. CONCLUSIONS: To influence medical students' professional identity construction, the authors advocate that educators seek change across the profession-faculty must acknowledge and take advantage of the tension between the discourses of standardization and diversity.

Discovery and synthesis of novel 4-aminopyrrolopyrimidine Tie-2 kinase inhibitors for the treatment of solid tumors.

The synthesis and biological evaluation of novel Tie-2 kinase inhibitors are presented. Based on the pyrrolopyrimidine chemotype, several new series are described, including the benzimidazole series by linking a benzimidazole to the C5-position of the 4-amino-pyrrolopyrimidine core and the ketophenyl series synthesized by incorporating a ketophenyl group to the C5-position. Medicinal chemistry efforts led to potent Tie-2 inhibitors. Compound 15, a ketophenyl pyrrolopyrimidine urea analog with improved physicochemical properties, demonstrated favorable in vitro attributes as well as dose responsive and robust oral tumor growth inhibition in animal models.

Enantioselective synthesis of nicotinic receptor probe 7,8-difluoro-1,2,3,4,5,6- hexahydro-1,5-methano-3-benzazocine.

[Structure: see text] The development of a concise enantioselective synthesis of nicotinic alkaloid 1 is presented. The route features the synthesis and use of a "stable" aliphatic triflate 21 in an alkylation step to generate Heck precursor 24 and an enantioselective cyclization to establish a compound with the key [3.2.1]-bicyclic core, 29.

A tale of two controversies: defining both the role of peroxidases in nitrotyrosine formation in vivo using eosinophil peroxidase and myeloperoxidase-deficient mice, and the nature of peroxidase-generated reactive nitrogen species.

Nitrotyrosine is widely used as a marker of post-translational modification by the nitric oxide ((.)NO, nitrogen monoxide)-derived oxidant peroxynitrite (ONOO(-)). However, since the discovery that myeloperoxidase (MPO) and eosinophil peroxidase (EPO) can generate nitrotyrosine via oxidation of nitrite (NO(2)(-)), several questions have arisen. First, the relative contribution of peroxidases to nitrotyrosine formation in vivo is unknown. Further, although evidence suggests that the one-electron oxidation product, nitrogen dioxide ((*)NO(2)), is the primary species formed, neither a direct demonstration that peroxidases form this gas nor studies designed to test for the possible concomitant formation of the two-electron oxidation product, ONOO(-), have been reported. Using multiple distinct models of acute inflammation with EPO- and MPO-knockout mice, we now demonstrate that leukocyte peroxidases participate in nitrotyrosine formation in vivo. In some models, MPO and EPO played a dominant role, accounting for the majority of nitrotyrosine formed. However, in other leukocyte-rich acute inflammatory models, no contribution for either MPO or EPO to nitrotyrosine formation could be demonstrated. Head-space gas analysis of helium-swept reaction mixtures provides direct evidence that leukocyte peroxidases catalytically generate (*)NO(2) formation using H(2)O(2) and NO(2)(-) as substrates. However, formation of an additional oxidant was suggested since both enzymes promote NO(2)(-)-dependent hydroxylation of targets under acidic conditions, a chemical reactivity shared with ONOO(-) but not (*)NO(2). Collectively, our results demonstrate that: 1) MPO and EPO contribute to tyrosine nitration in vivo; 2) the major reactive nitrogen species formed by leukocyte peroxidase-catalyzed oxidation of NO(2)(-) is the one-electron oxidation product, (*)NO(2); 3) as a minor reaction, peroxidases may also catalyze the two-electron oxidation of NO(2)(-), producing a ONOO(-)-like product. We speculate that the latter reaction generates a labile Fe-ONOO complex, which may be released following protonation under acidic conditions such as might exist at sites of inflammation.