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This study examines the role of several key features of effective professional development in changes in teachers’ mathematical knowledge needed for quality teaching. All activities of 568 teachers completed as part of the Math and Science Partnership programs were coded based on the core features identified in earlier literature and participating teachers’ mathematical knowledge were captured by valid teacher content knowledge instruments. Results of two-level hierarchical linear models provided insights on which form (e.g., study group or workshop), what content knowledge was addressed (e.g., general pedagogy, pedagogical content knowledge, knowledge of curriculum and standard), and how the activities were designed (e.g., examining student work and solving math problems) were related to gain in teachers’ mathematical knowledge.